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Home / Equine Research Bank / Front Immunol / A peptide mimic of SOCS1 modulates equine peripheral immune ...
Frontiers in immunology2025; 15; 1513157; doi: 10.3389/fimmu.2024.1513157

A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis.

Abstract: Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases. Topical administration of SOCS1-KIR, a peptide mimic of SOCS1, was previously correlated to reduced ocular pathologies within ERU patients. Unassigned: To further assess the translational potential of a SOCS1 mimetic to treat RU, we assessed peptide-mediated modulation of immune functions in vitro, using equine peripheral blood mononuclear cells (PBMC), and in vivo through topical administration of SOCS1-KIR into the eyes of experimental (non-uveitic) horses. Equine PBMCs from non-uveitic control and ERU horses were cultured with or without SOCS1-KIR pretreatment, followed by 72 hours of mitogen stimulation. Proliferation was assessed using MTT, and cytokine production within cell supernatants was assessed by Luminex. SOCS1-KIR or carrier eye-drops were topically applied to experimental horse eyes twice daily for 21 days, followed by enucleation and isolation of ocular aqueous and vitreous humor. Histology was used to assess peptide treatment safety and localization within treated equine eyes. Cytokine secretion within aqueous humor and vitreous, isolated from experimental equine eyes, was measured by Luminex. Unassigned: Following SOCS1-KIR pretreatment, cell proliferation significantly decreased in control, but not ERU-derived PBMCs. Despite differential regulation of cellular proliferation, SOCS1-KIR significantly reduced TNFα and IL-10 secretion in PHA-stimulated control and ERU equine PBMC. SOCS1-KIR increased PBMC secretion of IL-8. Topically administered SOCS1-KIR was well tolerated. Although SOCS1-KIR was undetectable within the eye, topically treated equine eyes had significant reductions in TNFα and IL-10. Interestingly, we found that while SOCS1-KIR treatment reduced TNFα and IL-10 production in healthy and ERU PBMC, SOCS1-KIR differentially modulated proliferation, IP-10 production, and RANTES within these two groups suggesting possible differences in cell types or activation status. Unassigned: Topical administration of a SOCS1 peptide mimic is safe to the equine eye and reduces ERU associated cytokines IL-10 and TNFα serving as potential biomarkers of drug efficacy in a future clinical trial.
Copyright © 2025 Stafford, Plummer, Smith, Gibson, Sharma, Vicuna, Diakite and Larkin.
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Publication Date: 2025-01-10 PubMed ID: 39867889PubMed Central: PMC11757128DOI: 10.3389/fimmu.2024.1513157Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research evaluates the potential of a protein mimetic, SOCS1-KIR, to treat recurrent uveitis (RU), an autoimmune eye disease, in horses and implicitly humans. The study found that this treatment, when topically applied, can safely regulate immune responses in the eye.

Introduction and Objectives

  • This study explores the effects of a protein mimic, SOCS1-KIR, in treating recurrent uveitis (RU). RU is an autoimmune disease that significantly impacts the vision of humans and horses. The focus of the study was on equine and human RU due to their peculiar commonalities, such as spontaneous occurrence of the disease and abnormal cytokine signaling.
  • The driving factor in choosing SOCS1-KIR for the study is the role the native protein, SOCS1, plays in regulating cytokine signaling. It has been noted that lower levels of SOCS1 are found in numerous autoimmune diseases.
  • SOCS1-KIR’s efficacy had previously been observed when it was applied topically, leading to reduced pathological ocular symptoms in patients suffering from equine recurrent uveitis (ERU).
  • The primary objective was to further confirm the potential usage of a SOCS1 mimetic to treat RU by assessing the modulation of immune functions of the mimic on equine peripheral blood mononuclear cells (PBMC). The team also aimed to observe the local effects within the eyes of experimental non-uveitic horses after topical administration of SOCS1-KIR.

Methodology

  • The investigation used PBMCs from non-uveitic control and ERU horses. These cells were cultured with or without pretreatment with the SOCS1-KIR peptide. The team then stimulated the samples with mitogens for 72 hours.
  • Multiple techniques were used to assess the effects of the pretreatment. MTT testing was used to evaluate cell proliferation while Luminex testing was performed on the supernatant from the cell cultures to evaluate cytokine production.
  • For the in vivo experiment, topical application of the SOCS1-KIR peptide (or a carrier-only control) was given to the eyes of experimental horses. This treatment was given twice per day for a 21-day period, followed by isolation of humors from the eyes and evaluation via histological analysis to assess treatment safety and localization of the peptide in the treated eyes.

Results

  • After pretreatment with SOCS1-KIR, noticeable reductions in cell proliferation were observed in control samples, but not in ERU-derived PBMCs. Nevertheless, the peptide significantly reduced TNFα and IL-10 secretion in both types of stimulated cells and increased production of IL-8.
  • Topical application of the SOCS1-KIR peptide was well-tolerated by the experimental horses’ eyes. Despite not being detectable within the eye, it was found that topically treated eyes exhibited significant reduction in TNFα and IL-10.

Conclusions

  • The investigation concludes that topical administration of the SOCS1 peptide mimic is safe for the eyes of horses and leads to a reduction in the cytokines IL-10 and TNFα, known to be associated with ERU. These cytokines could potentially be used as biomarkers for drug efficacy in future clinical trials.

Cite This Article

APA
Stafford LS, Plummer CE, Smith WC, Gibson DJ, Sharma J, Vicuna V, Diakite S, Larkin J. (2025). A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis. Front Immunol, 15, 1513157. https://doi.org/10.3389/fimmu.2024.1513157

Publication

Frontiers in immunology
ISSN: 1664-3224
NlmUniqueID: 101560960
Country: Switzerland
Language: English
Volume: 15
Pages: 1513157

Researcher Affiliations

Stafford, Lauren Stewart
  • Microbiology and Cell Science, Institute of Food and Agricultural Science, University of Florida, Gainesville, FL, United States.
Plummer, Caryn E
  • Departments of Large and Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.
Smith, W Clay
  • Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, FL, United States.
Gibson, Daniel J
  • Capstone College of Nursing, University of Alabama, Tuscaloosa, AL, United States.
Sharma, Jatin
  • Microbiology and Cell Science, Institute of Food and Agricultural Science, University of Florida, Gainesville, FL, United States.
Vicuna, Valeria
  • Microbiology and Cell Science, Institute of Food and Agricultural Science, University of Florida, Gainesville, FL, United States.
Diakite, Sisse
  • Microbiology and Cell Science, Institute of Food and Agricultural Science, University of Florida, Gainesville, FL, United States.
Larkin, Joseph
  • Microbiology and Cell Science, Institute of Food and Agricultural Science, University of Florida, Gainesville, FL, United States.

MeSH Terms

  • Animals
  • Horses
  • Uveitis / immunology
  • Uveitis / drug therapy
  • Uveitis / veterinary
  • Suppressor of Cytokine Signaling 1 Protein / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Horse Diseases / immunology
  • Horse Diseases / drug therapy
  • Cytokines / metabolism
  • Peptides / pharmacology
  • Recurrence
  • Cells, Cultured

Grant Funding

  • S10 OD028476 / NIH HHS

Conflict of Interest Statement

JL3 is co-inventor on a patent, held by the University of Florida, on the SOCS mimetic technology, which is currently under licensing agreement to Arctic Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 118 references
  1. Kulbrock M, Lehner S, Metzger J, Ohnesorge B, Distl O. A genome-wide association study identifies risk loci to equine recurrent uveitis in German warmblood horses.. PloS One (2013) 8:e71619.
    doi: 10.1371/journal.pone.0071619pmc: PMC3743750pubmed: 23977091google scholar: lookup
  2. Plummer CE, Polk T, Sharma J, Bae SS, Barr O, Jones A. Open label safety and efficacy pilot to study mitigation of equine recurrent uveitis through topical suppressor of cytokine signaling-1 mimetic peptide.. Sci Rep (2022) 12:7177.
    doi: 10.1038/s41598-022-11338-xpmc: PMC9065145pubmed: 35505065google scholar: lookup
  3. Witkowski L, Cywinska A, Paschalis-Trela K, Crisman M, Kita J. Multiple etiologies of equine recurrent uveitis - A natural model for human autoimmune uveitis: A brief review.. Comp Immunol Microbiol Infect Dis (2016) 44:14–20.
    doi: 10.1016/j.cimid.2015.11.004pubmed: 26851589google scholar: lookup
  4. Sandmeyer LS, Bellone R. Inherited ocular disorders.. Equine Ophthalmology: Third Edition Wiley Online Books; (2016).
    doi: 10.1002/9781119047919.ch13google scholar: lookup
  5. Allbaugh RA. Equine recurrent uveitis: A review of clinical assessment and management.. Equine Vet Educ (2017) 29:279–88.
    doi: 10.1111/eve.12548google scholar: lookup
  6. Curling A. Equine recurrent uveitis: classification, etiology, and pathogenesis.. Compend Contin Educ Vet (2011) 33:E2.
    pubmed: 21870351
  7. He C, Yu C-R, Sun L, Mahdi RM, Larkin J, Egwuagu CE. Topical administration of a suppressor of cytokine signaling-1 (SOCS1) mimetic peptide inhibits ocular inflammation and mitigates ocular pathology during mouse uveitis.. J Autoimmun (2015) 62:31–8.
    doi: 10.1016/j.jaut.2015.05.011pmc: PMC4529792pubmed: 26094775google scholar: lookup
  8. Malalana F, Stylianides A, McGowan C. Equine recurrent uveitis: Human and equine perspectives.. Veterinary J (2015) 206:22–9.
    doi: 10.1016/j.tvjl.2015.06.017pubmed: 26188862google scholar: lookup
  9. Gerding JC, Gilger BC. Prognosis and impact of equine recurrent uveitis.. Equine Vet J (2016) 48:290–8.
    doi: 10.1111/evj.12451pubmed: 25891653google scholar: lookup
  10. Sandmeyer LS, Bauer BS, Feng CX, Grahn BH. Equine recurrent uveitis in western Canadian prairie provinces: A retrospective study (2002-2015).. Can Vet J (2017) 58:717–22.
    pmc: PMC5501119pubmed: 28698690
  11. He C, Yu C-R, Mattapallil MJ, Sun L, Larkin IIIJ, Egwuagu CE. SOCS1 mimetic peptide suppresses chronic intraocular inflammatory disease (Uveitis).. Mediators Inflammation (2016) 2016:1–15.
    doi: 10.1155/2016/2939370pmc: PMC5040805pubmed: 27703302google scholar: lookup
  12. Caspi RR. A look at autoimmunity and inflammation in the eye.. J Clin Invest (2010) 120:3073–83.
    doi: 10.1172/JCI42440pmc: PMC2929721pubmed: 20811163google scholar: lookup
  13. Saldinger LK, Nelson SG, Bellone RR, Lassaline M, Mack M, Walker NJ. Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells.. Vitro Vet Ophthalmol (2020) 23:160–70.
    doi: 10.1111/vop.12704pmc: PMC6980227pubmed: 31441218google scholar: lookup
  14. Deeg CA, Hauck SM, Amann B, Pompetzki D, Altmann F, Raith A. Equine recurrent uveitis – A spontaneous horse model of uveitis.. Ophthalmic Res (2008) 40:151–3.
    doi: 10.1159/000119867pubmed: 18421230google scholar: lookup
  15. Steinbach F, Deeg C, Mauel S, Wagner B. Equine immunology: offspring of the serum horse.. Trends Immunol (2002) 23:223–5.
    doi: 10.1016/S1471-4906(02)02193-2pubmed: 12102731google scholar: lookup
  16. Barfüßer C, Wiedemann C, Hoffmann ALC, Hirmer S, Deeg CA. Altered metabolic phenotype of immune cells in a spontaneous autoimmune uveitis model.. Front Immunol (2021) 12:601619.
    doi: 10.3389/fimmu.2021.601619pmc: PMC8353246pubmed: 34385998google scholar: lookup
  17. Degroote RL, Hauck SM, Amann B, Hirmer S, Ueffing M, Deeg CA. Unraveling the equine lymphocyte proteome: differential septin 7 expression associates with immune cells in equine recurrent uveitis.. PloS One (2014) 9:e91684.
    doi: 10.1371/journal.pone.0091684pmc: PMC3951111pubmed: 24614191google scholar: lookup
  18. Deeg CA, Ehrenhofer M, Thurau SR, Reese S, Wildner G, Kaspers B. Immunopathology of recurrent uveitis in spontaneously diseased horses.. Exp Eye Res (2002) 75:127–33.
    doi: 10.1006/exer.2002.2011pubmed: 12137758google scholar: lookup
  19. Kingsley NB, Sandmeyer L, Bellone RR. A review of investigated risk factors for developing equine recurrent uveitis.. Vet Ophthalmol (2022) 26:86–100.
    doi: 10.1111/vop.13002pubmed: 35691017google scholar: lookup
  20. Fingerhut L, Ohnesorge B, von Borstel M, Schumski A, Strutzberg-Minder K, Mörgelin M. Neutrophil extracellular traps in the pathogenesis of equine recurrent uveitis (ERU).. Cells (2019) 8:1528.
    doi: 10.3390/cells8121528pmc: PMC6953072pubmed: 31783639google scholar: lookup
  21. Lee RW, Nicholson LB, Sen HN, Chan C-C, Wei L, Nussenblatt RB. Autoimmune and autoinflammatory mechanisms in uveitis.. Semin Immunopathol (2014) 36:581–94.
    doi: 10.1007/s00281-014-0433-9pmc: PMC4186974pubmed: 24858699google scholar: lookup
  22. Gilger BC, Michau TM. Equine recurrent uveitis: new methods of management.. Vet Clin North Am Equine Pract (2004) 20:417–27.
    doi: 10.1016/j.cveq.2004.04.010pubmed: 15271431google scholar: lookup
  23. Guly CM, Forrester JV. Investigation and management of uveitis.. BMJ (2010) 341:c4976–6.
    doi: 10.1136/bmj.c4976pubmed: 20943722google scholar: lookup
  24. Wu X, Tao M, Zhu L, Zhang T, Zhang M. Pathogenesis and current therapies for non-infectious uveitis.. Clin Exp Med (2022) 23:1089–106.
    doi: 10.1007/s10238-022-00954-6pmc: PMC10390404pubmed: 36422739google scholar: lookup
  25. Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease.. Br J Ophthalmol (1996) 80:332–6.
    doi: 10.1136/bjo.80.4.332pmc: PMC505460pubmed: 8703885google scholar: lookup
  26. Hassan M, Karkhur S, Bae JH, Halim MS, Ormaechea MS, Onghanseng N. New therapies in development for the management of non-infectious uveitis: A review.. Clin Exp Ophthalmol (2019) 47:396–417.
    doi: 10.1111/ceo.13511pubmed: 30938012google scholar: lookup
  27. Gilger BC, Malok E, Cutter KV, Stewart T, Horohov DW, Allen JB. Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis.. Vet Immunol Immunopathol (1999) 71:17–28.
    doi: 10.1016/s0165-2427(99)00082-3pubmed: 10522783google scholar: lookup
  28. Degroote RL, Deeg CA. Immunological insights in equine recurrent uveitis.. Front Immunol (2021) 11:609855.
    doi: 10.3389/fimmu.2020.609855pmc: PMC7821741pubmed: 33488614google scholar: lookup
  29. Lazarevic V, Glimcher LH, Lord GM. T-bet: a bridge between innate and adaptive immunity.. Nat Rev Immunol (2013) 13:777–89.
    doi: 10.1038/nri3536pmc: PMC6290922pubmed: 24113868google scholar: lookup
  30. Ooi KG-J, Galatowicz G, Calder VL, Lightman SL. Cytokines and chemokines in uveitis - is there a correlation with clinical phenotype?. Clin Med Res (2006) 4:294–309.
    doi: 10.3121/cmr.4.4.294pmc: PMC1764804pubmed: 17210978google scholar: lookup
  31. Horai R, Caspi RR. Cytokines in autoimmune uveitis.. J Interferon Cytokine Res (2011) 31:733–44.
    doi: 10.1089/jir.2011.0042pmc: PMC3189550pubmed: 21787221google scholar: lookup
  32. Chilson OP, Boylston AW, Crumpton MJ. Phaseolus vulgaris phytohaemagglutinin (PHA) binds to the human T lymphocyte antigen receptor.. EMBO J (1984) 3:3239–45.
    doi: 10.1002/j.1460-2075.1984.tb02285.xpmc: PMC557844pubmed: 6335429google scholar: lookup
  33. Schneider OD, Millen SH, Weiss AA, Miller WE. Mechanistic insight into pertussis toxin and lectin signaling using T cells engineered to express a CD8α/CD3ζ Chimeric receptor.. Biochemistry (2012) 51:4126–37.
    doi: 10.1021/bi3002693pmc: PMC3359064pubmed: 22551306google scholar: lookup
  34. Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects.. Drugs (2017) 77:521–46.
    doi: 10.1007/s40265-017-0701-9pmc: PMC7102286pubmed: 28255960google scholar: lookup
  35. Sharma J, Larkin J. Therapeutic implication of SOCS1 modulation in the treatment of autoimmunity and cancer.. Front Pharmacol (2019) 10:324.
    doi: 10.3389/fphar.2019.00324pmc: PMC6499178pubmed: 31105556google scholar: lookup
  36. Hadjadj J, Castro CN, Tusseau M, Stolzenberg M-C, Mazerolles F, Aladjidi N. Early-onset autoimmunity associated with SOCS1 haploinsufficiency.. Nat Commun (2020) 11:5341.
    doi: 10.1038/s41467-020-18925-4pmc: PMC7578789pubmed: 33087723google scholar: lookup
  37. Hu K, Hou S, Jiang Z, Kijlstra A, Yang P. JAK2 and STAT3 polymorphisms in a han chinese population with behçet’s disease.. Invest Opthalmol Visual Sci (2012) 53:538.
    doi: 10.1167/iovs.11-8440pubmed: 22205606google scholar: lookup
  38. Su G, Zhong Z, Zhou Q, Du L, Ye Z, Li F. Identification of novel risk loci for behçet’s disease–related uveitis in a chinese population in a genome-wide association study.. Arthritis Rheumatol (2022) 74:671–81.
    doi: 10.1002/art.41998pubmed: 34652073google scholar: lookup
  39. Tulunay A, Dozmorov MG, Ture-Ozdemir F, Yilmaz V, Eksioglu-Demiralp E, Alibaz-Oner F. Activation of the JAK/STAT pathway in Behcet’s disease.. Genes Immun (2015) 16:170–5.
    doi: 10.1038/gene.2014.64pmc: PMC4443896pubmed: 25410656google scholar: lookup
  40. Hou S, Qi J, Zhang Q, Liao D, Li Q, Hu K. Genetic variants in the JAK1 gene confer higher risk of Behcet’s disease with ocular involvement in Han Chinese.. Hum Genet (2013) 132:1049–58.
    doi: 10.1007/s00439-013-1312-5pubmed: 23674219google scholar: lookup
  41. Hu X, li J, Fu M, Zhao X, Wang W. The JAK/STAT signaling pathway: from bench to clinic.. Signal Transduct Target Ther (2021) 6:402.
    doi: 10.1038/s41392-021-00791-1pmc: PMC8617206pubmed: 34824210google scholar: lookup
  42. Morris R, Kershaw NJ, Babon JJ. The molecular details of cytokine signaling via the JAK/STAT pathway.. Protein Sci (2018) 27:1984–2009.
    doi: 10.1002/pro.3519pmc: PMC6237706pubmed: 30267440google scholar: lookup
  43. Ahmed CM, Massengill MT, Brown EE, Ildefonso CJ, Johnson HM, Lewin AS. A cell penetrating peptide from SOCS-1 prevents ocular damage in experimental autoimmune uveitis.. Exp Eye Res (2018) 177:12–22.
    doi: 10.1016/j.exer.2018.07.020pmc: PMC6528831pubmed: 30048621google scholar: lookup
  44. La Manna S, Lopez-Sanz L, Bernal S, Jimenez-Castilla L, Prieto I, Morelli G. Antioxidant effects of PS5, a peptidomimetic of suppressor of cytokine signaling 1, in experimental atherosclerosis.. Antioxidants (2020) 9:754.
    doi: 10.3390/antiox9080754pmc: PMC7465353pubmed: 32824091google scholar: lookup
  45. Madonna S, Scarponi C, Doti N, Carbone T, Cavani A, Scognamiglio PL. Therapeutical potential of a peptide mimicking the SOCS 1 kinase inhibitory region in skin immune responses.. Eur J Immunol (2013) 43:1883–95.
    doi: 10.1002/eji.201343370pubmed: 23592500google scholar: lookup
  46. Sharma J, Collins TD, Roach T, Mishra S, Lam BK, Mohamed ZS. Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.. Sci Rep (2021) 11:6354.
    doi: 10.1038/s41598-021-86017-4pmc: PMC7973732pubmed: 33737712google scholar: lookup
  47. Ahmed CMI, Larkin J, Johnson HM. SOCS1 mimetics and antagonists: A complementary approach to positive and negative regulation of immune function.. Front Immunol (2015) 6:183.
    doi: 10.3389/fimmu.2015.00183pmc: PMC4404822pubmed: 25954276google scholar: lookup
  48. Ahmed CM, Patel AP, Ildefonso CJ, Johnson HM, Lewin AS. Corneal application of r9-socs1-kir peptide alleviates endotoxin-induced uveitis.. Transl Vis Sci Technol (2021) 10.
    doi: 10.1167/tvst.10.3.25pmc: PMC7995917pubmed: 34003962google scholar: lookup
  49. Hernández C, Bogdanov P, Gómez-Guerrero C, Sampedro J, Solà-Adell C, Espejo C. SOCS1-derived peptide administered by eye drops prevents retinal neuroinflammation and vascular leakage in experimental diabetes.. Int J Mol Sci (2019) 20:3615.
    doi: 10.3390/ijms20153615pmc: PMC6695852pubmed: 31344857google scholar: lookup
  50. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.. J Immunol Methods (1983) 65:55–63.
    doi: 10.1016/0022-1759(83)90303-4pubmed: 6606682google scholar: lookup
  51. Duran MC, Willenbrock S, Müller J-MV, Nolte I, Feige K, Murua Escobar H. Establishment and evaluation of a bead-based luminex assay allowing simultaneous quantification of equine IL-12 and IFN-γ.. Anticancer Res (2013) 33:1325–36.
    pubmed: 23564769
  52. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T. Fiji: an open-source platform for biological-image analysis.. Nat Methods (2012) 9:676–82.
    doi: 10.1038/nmeth.2019pmc: PMC3855844pubmed: 22743772google scholar: lookup
  53. Xu L, Bolch SN, Santiago CP, Dyka FM, Akil O, Lobanova ES. Clarin-1 expression in adult mouse and human retina highlights a role of Müller glia in Usher syndrome.. J Pathol (2020) 250:195–204.
    doi: 10.1002/path.5360pmc: PMC7003947pubmed: 31625146google scholar: lookup
  54. Valcarce V, Stafford LS, Neu J, Parker L, Vicuna V, Cross T. COVID-19 booster enhances IgG mediated viral neutralization by human milk.. Vitro Front Nutr (2024) 11:1289413.
    doi: 10.3389/fnut.2024.1289413pmc: PMC10884187pubmed: 38406184google scholar: lookup
  55. Norian R, Delirezh N, Azadmehr A. Evaluation of proliferation and cytokines production by mitogen-stimulated bovine peripheral blood mononuclear cells.. Vet Res Forum (2015) 6:265–71.
    pmc: PMC4769330pubmed: 26973760
  56. Collins EL, Jager LD, Dabelic R, Benitez P, Holdstein K, Lau K. Inhibition of SOCS1 –/– lethal autoinflammatory disease correlated to enhanced peripheral foxp3 + Regulatory T cell homeostasis.. J Immunol (2011) 187:2666–76.
    doi: 10.4049/jimmunol.1003819pmc: PMC3159835pubmed: 21788442google scholar: lookup
  57. Gilger BC, Yang P, Salmon JH, Jaffe GJ, Allen JB. Expression of a chemokine by ciliary body epithelium in horses with naturally occurring recurrent uveitis and in cultured ciliary body epithelial cells.. Am J Vet Res (2002) 63:942–7.
    doi: 10.2460/ajvr.2002.63.942pubmed: 12118672google scholar: lookup
  58. Curto E, Messenger KM, Salmon JH, Gilger BC. Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis.. Vet Immunol Immunopathol (2016) 182:43–51.
    doi: 10.1016/j.vetimm.2016.09.008pubmed: 27863549google scholar: lookup
  59. Takase H, Futagami Y, Yoshida T, Kamoi K, Sugita S, Imai Y. Cytokine profile in aqueous humor and sera of patients with infectious or noninfectious uveitis.. Invest Ophthalmol Vis Sci (2006) 47:1557–61.
    doi: 10.1167/iovs.05-0836pubmed: 16565392google scholar: lookup
  60. El-Asrar AMA, Struyf S, Kangave D, Al-Obeidan SS, Opdenakker G, Geboes K. Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis.. Clin Immunol (2011) 139:177–84.
    doi: 10.1016/j.clim.2011.01.014pubmed: 21334264google scholar: lookup
  61. Bonacini M, Soriano A, Cimino L, De Simone L, Bolletta E, Gozzi F. Cytokine profiling in aqueous humor samples from patients with non-infectious uveitis associated with systemic inflammatory diseases.. Front Immunol (2020) 11:358.
    doi: 10.3389/fimmu.2020.00358pmc: PMC7077343pubmed: 32210963google scholar: lookup
  62. Armstrong L, Jordan N, Millar A. Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes.. Thorax (1996) 51:143–9.
    doi: 10.1136/thx.51.2.143pmc: PMC473022pubmed: 8711645google scholar: lookup
  63. Luster AD, Unkeless JC, Ravetch JV. [amp]]gamma;-Interferon transcriptionally regulates an early-response gene containing homology to platelet proteins.. Nature (1985) 315:672–6.
    doi: 10.1038/315672a0pubmed: 3925348google scholar: lookup
  64. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD. IFN-γ-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking.. J Immunol (2002) 168:3195–204.
    doi: 10.4049/jimmunol.168.7.3195pubmed: 11907072google scholar: lookup
  65. Sancéau J, Falcoff R, Beranger F, Carter DB, Wietzerbin J. Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha.. Immunology (1990) 69:52–6.
    pmc: PMC1385719pubmed: 1690177
  66. Valentincic NV, de Groot-Mijnes JDF, Kraut A, Korosec P, Hawlina M, Rothova A. Intraocular and serum cytokine profiles in patients with intermediate uveitis.. Mol Vis (2011) 17:2003–10.
    pmc: PMC3154134pubmed: 21850175
  67. Hoffmann ALC, Hauck SM, Deeg CA, Degroote RL. Pre-activated granulocytes from an autoimmune uveitis model show divergent pathway activation profiles upon IL8 stimulation.. In Vitro Int J Mol Sci (2022) 23:9555.
    doi: 10.3390/ijms23179555pmc: PMC9455241pubmed: 36076947google scholar: lookup
  68. Takase H, Yu C-R, Liu X, Fujimoto C, Gery I, Egwuagu CE. Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): Potential neuroprotective role of SOCS proteins.. J Neuroimmunol (2005) 168:118–27.
    doi: 10.1016/j.jneuroim.2005.07.021pubmed: 16154209google scholar: lookup
  69. Takeuchi M, Usui Y, Okunuki Y, Zhang L, Ma J, Yamakawa N. Immune responses to interphotoreceptor retinoid-binding protein and S-antigen in behçet’s patients with uveitis.. Invest Opthalmol Visual Sci (2010) 51:3067.
    doi: 10.1167/iovs.09-4313pubmed: 20089879google scholar: lookup
  70. Kleiveland CR. Peripheral blood mononuclear cells.. The Impact of Food Bioactives on Health Springer International Publishing, Cham: (2015). p. 161–7.
    doi: 10.1007/978-3-319-16104-4_15google scholar: lookup
  71. Watson JL, Stott JL, Blanchard MT, Lavoie J-P, Wilson WD, Gershwin LJ. Phenotypic characterization of lymphocyte subpopulations in horses affected with chronic obstructive pulmonary disease and in normal controls.. Vet Pathol (1997) 34:108–16.
    doi: 10.1177/030098589703400203pubmed: 9066077google scholar: lookup
  72. Lumsden JH, Rowe R, Mullen K. Hematology and biochemistry reference values for the light horse.. Can J Comp Med (1980) 44:32–42.
    pmc: PMC1320032pubmed: 7397597
  73. Patel RS, Tomlinson JE, Divers TJ, Van de Walle GR, Rosenberg BR. Single-cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse cell types including T-bet+ B cells.. BMC Biol (2021) 19:13.
    doi: 10.1186/s12915-020-00947-5pmc: PMC7820527pubmed: 33482825google scholar: lookup
  74. Chaiwut R, Kasinrerk W. Very low concentration of lipopolysaccharide can induce the production of various cytokines and chemokines in human primary monocytes.. BMC Res Notes (2022) 15:42.
    doi: 10.1186/s13104-022-05941-4pmc: PMC8832778pubmed: 35144659google scholar: lookup
  75. Lawlor N, Nehar-Belaid D, Grassmann JDS, Stoeckius M, Smibert P, Stitzel ML. Single cell analysis of blood mononuclear cells stimulated through either LPS or anti-CD3 and anti-CD28.. Front Immunol (2021) 12:636720.
    doi: 10.3389/fimmu.2021.636720pmc: PMC8010670pubmed: 33815388google scholar: lookup
  76. Schnabel CL, Babasyan S, Freer H, Larson EM, Wagner B. New mAbs facilitate quantification of secreted equine TNF-α and flow cytometric analysis in monocytes and T cells.. Vet Immunol Immunopathol (2021) 238:110284.
    doi: 10.1016/j.vetimm.2021.110284pubmed: 34126553google scholar: lookup
  77. Holbrook J, Lara-Reyna S, Jarosz-Griffiths H, McDermott MF. Tumour necrosis factor signalling in health and disease.. F1000Res (2019) 8:111.
    doi: 10.12688/f1000research.17023.1pmc: PMC6352924pubmed: 30755793google scholar: lookup
  78. Grivennikov SI, Tumanov AV, Liepinsh DJ, Kruglov AA, Marakusha BI, Shakhov AN. Distinct and nonredundant in vivo functions of TNF produced by T cells and macrophages/neutrophils.. Immunity (2005) 22:93–104.
    doi: 10.1016/j.immuni.2004.11.016pubmed: 15664162google scholar: lookup
  79. Roberts CA, Durham LE, Fleskens V, Evans HG, Taams LS. TNF blockade maintains an IL-10+ Phenotype in human effector CD4+ and CD8+ T cells.. Front Immunol (2017) 8:157.
    doi: 10.3389/fimmu.2017.00157pmc: PMC5309392pubmed: 28261215google scholar: lookup
  80. Taylor PC, Feldmann M. Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis.. Nat Rev Rheumatol (2009) 5:578–82.
    doi: 10.1038/nrrheum.2009.181pubmed: 19798034google scholar: lookup
  81. Mirshahi A, Hoehn R, Lorenz K, Kramann C, Baatz H. Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts.. J Ophthalmic Vis Res (2012) 7:39–44.
    pmc: PMC3381107pubmed: 22737386
  82. Chinen T, Kobayashi T, Ogata H, Takaesu G, Takaki H, Hashimoto M. Suppressor of cytokine signaling-1 regulates inflammatory bowel disease in which both IFNγ and IL-4 are involved.. Gastroenterology (2006) 130:373–88.
    doi: 10.1053/j.gastro.2005.10.051pubmed: 16472593google scholar: lookup
  83. Sun K, Salmon S, Yajjala VK, Bauer C, Metzger DW. Expression of suppressor of cytokine signaling 1 (SOCS1) impairs viral clearance and exacerbates lung injury during influenza infection.. PloS Pathog (2014) 10:e1004560.
    doi: 10.1371/journal.ppat.1004560pmc: PMC4263766pubmed: 25500584google scholar: lookup
  84. Chen Y, Zhong W, Xie Z, Li B, Li H, Gao K. Suppressor of cytokine signaling 1 (SOCS1) inhibits antiviral responses to facilitate Senecavirus A infection by regulating the NF-κB signaling pathway.. Virus Res (2022) 313:198748.
    doi: 10.1016/j.virusres.2022.198748pubmed: 35304133google scholar: lookup
  85. Morita Y, Naka T, Kawazoe Y, Fujimoto M, Narazaki M, Nakagawa R. Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblasts.. Proc Natl Acad Sci (2000) 97:5405–10.
    doi: 10.1073/pnas.090084797pmc: PMC25841pubmed: 10792035google scholar: lookup
  86. Kimura A. SOCS-1 suppresses TNF- -induced apoptosis through the regulation of Jak activation.. Int Immunol (2004) 16:991–9.
    doi: 10.1093/intimm/dxh102pubmed: 15173123google scholar: lookup
  87. Strebovsky J, Walker P, Lang R, Dalpke AH. Suppressor of cytokine signaling 1 (SOCS1) limits NFκB signaling by decreasing p65 stability within the cell nucleus.. FASEB J (2011) 25:863–74.
    doi: 10.1096/fj.10-170597pubmed: 21084693google scholar: lookup
  88. Jha A, Larkin J, Moore E. SOCS1-KIR peptide in PEGDA hydrogels reduces pro-inflammatory macrophage activation.. Macromol Biosci (2023) 23.
    doi: 10.1002/mabi.202300237pubmed: 37337867google scholar: lookup
  89. He Y, Zhang W, Zhang R, Zhang H, Min W. SOCS1 inhibits tumor necrosis factor-induced activation of ASK1-JNK inflammatory signaling by mediating ASK1 degradation.. J Biol Chem (2006) 281:5559–66.
    doi: 10.1074/jbc.M512338200pubmed: 16407264google scholar: lookup
  90. Mori K, Kinoshita S. The role of TNF-α in retinal degeneration and repair.. J Ophthalmic Inflammation Infect (2006) 17:300–10.
  91. Mac Nair CE, Fernandes KA, Schlamp CL, Libby RT, Nickells RW. Tumor necrosis factor alpha has an early protective effect on retinal ganglion cells after optic nerve crush.. J Neuroinflamm (2014) 11:194.
    doi: 10.1186/s12974-014-0194-3pmc: PMC4245774pubmed: 25407441google scholar: lookup
  92. Fontaine V, Mohand-Said S, Hanoteau N, Fuchs C, Pfizenmaier K, Eisel U. Neurodegenerative and neuroprotective effects of tumor necrosis factor (TNF) in retinal ischemia: opposite roles of TNF receptor 1 and TNF receptor 2.. J Neurosci (2002) 22:RC216–6.
    doi: 10.1523/JNEUROSCI.22-07-j0001.2002pmc: PMC6758303pubmed: 11917000google scholar: lookup
  93. Qazi BS, Tang K, Qazi A. Recent advances in underlying pathologies provide insight into interleukin-8 expression-mediated inflammation and angiogenesis.. Int J Inflam (2011) 2011:1–13.
    doi: 10.4061/2011/908468pmc: PMC3253461pubmed: 22235381google scholar: lookup
  94. Turner N, Mughal R, Warburton P, Oregan D, Ball S, Porter K. Mechanism of TNFα-induced IL-1α, IL-1β and IL-6 expression in human cardiac fibroblasts: Effects of statins and thiazolidinediones.. Cardiovasc Res (2007) 76:81–90.
    doi: 10.1016/j.cardiores.2007.06.003pubmed: 17612514google scholar: lookup
  95. Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M. IL-10, IL-6, and TNF-α: Central factors in the altered cytokine network of uremia—The good, the bad, and the ugly.. Kidney Int (2005) 67:1216–33.
    doi: 10.1111/j.1523-1755.2005.00200.xpubmed: 15780075google scholar: lookup
  96. Dhingra S, Sharma AK, Arora RC, Slezak J, Singal PK. IL-10 attenuates TNF- -induced NF B pathway activation and cardiomyocyte apoptosis.. Cardiovasc Res (2009) 82:59–66.
    doi: 10.1093/cvr/cvp040pubmed: 19181934google scholar: lookup
  97. van der Poll T, Jansen J, Levi M, ten Cate H, ten Cate JW, van Deventer SJ. Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees.. J Exp Med (1994) 180:1985–8.
    doi: 10.1084/jem.180.5.1985pmc: PMC2191735pubmed: 7964475google scholar: lookup
  98. Iyer SS, Cheng G. Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease.. Crit Rev Immunol (2012) 32:23–63.
    doi: 10.1615/CritRevImmunol.v32.i1.30pmc: PMC3410706pubmed: 22428854google scholar: lookup
  99. Torvinen M, Campwala H, Kilty I. The role of IFN-γ in regulation of IFN-γ-inducible protein 10 (IP-10) expression in lung epithelial cell and peripheral blood mononuclear cell co-cultures.. Respir Res (2007) 8:80.
    doi: 10.1186/1465-9921-8-80pmc: PMC2174934pubmed: 17996064google scholar: lookup
  100. Han X, Wei Q, Xu R-X, Wang S, Liu X-Y, Guo C. Minocycline induces tolerance to dendritic cell production probably by targeting the SOCS1/TLR4/NF-κB signaling pathway.. Transpl Immunol (2023) 79:101856.
    doi: 10.1016/j.trim.2023.101856pubmed: 37196867google scholar: lookup
  101. Frobøse H, Groth Rønn S, Heding PE, Mendoza H, Cohen P, Mandrup-Poulsen T. Suppressor of cytokine signaling-3 inhibits interleukin-1 signaling by targeting the TRAF-6/TAK1 complex.. Mol Endocrinol (2006) 20:1587–96.
    doi: 10.1210/me.2005-0301pubmed: 16543409google scholar: lookup
  102. Huang S, Liu K, Cheng A, Wang M, Cui M, Huang J. SOCS proteins participate in the regulation of innate immune response caused by viruses.. Front Immunol (2020) 11:558341.
    doi: 10.3389/fimmu.2020.558341pmc: PMC7544739pubmed: 33072096google scholar: lookup
  103. Han C, Fu J, Liu Z, Huang H, Luo L, Yin Z. Dipyrithione inhibits IFN-γ-induced JAK/STAT1 signaling pathway activation and IP-10/CXCL10 expression in RAW264.7 cells.. Inflammation Res (2010) 59:809–16.
    doi: 10.1007/s00011-010-0192-6pmc: PMC7079753pubmed: 20372968google scholar: lookup
  104. Siveke JT, Hamann A. T helper 1 and T helper 2 cells respond differentially to chemokines.. J Immunol (1998) 160:550–4.
    doi: 10.4049/jimmunol.160.2.550pubmed: 9551886google scholar: lookup
  105. Adamus G, Manczak M, Machnicki M. Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE.. Invest Ophthalmol Vis Sci (2001) 42:2894–903.
    pubmed: 11687534
  106. Lechner J, Chen M, Hogg RE, Toth L, Silvestri G, Chakravarthy U. Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8).. J Neuroinflamm (2017) 14:42.
    doi: 10.1186/s12974-017-0820-ypmc: PMC5324243pubmed: 28231837google scholar: lookup
  107. Aman MJ, Rudolf G, Goldschmitt J, Aulitzky WE, Lam C, Huber C. Type-I interferons are potent inhibitors of interleukin-8 production in hematopoietic and bone marrow stromal cells.. Blood (1993) 82:2371–8.
    doi: 10.1182/blood.V82.8.2371.2371pubmed: 8400288google scholar: lookup
  108. Khabar KSA, Al-Zoghaibi F, Al-Ahdal MN, Murayama T, Dhalla M, Mukaida N. The α Chemokine, interleukin 8, inhibits the antiviral action of interferon α.. J Exp Med (1997) 186:1077–85.
    doi: 10.1084/jem.186.7.1077pmc: PMC2199072pubmed: 9314556google scholar: lookup
  109. Choi AMK, Jacoby DB. Influenza virus A infection induces interleukin-8 gene expression in human airway epitheial cells.. FEBS Lett (1992) 309:327–9.
    doi: 10.1016/0014-5793(92)80799-Mpubmed: 1516705google scholar: lookup
  110. Fenner JE, Starr R, Cornish AL, Zhang J-G, Metcalf D, Schreiber RD. Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity.. Nat Immunol (2006) 7:33–9.
    doi: 10.1038/ni1287pubmed: 16311601google scholar: lookup
  111. Marega LF, Sabino JS, Pedroni MV, Teocchi M, Lanaro C, de Albuquerque DM. Phenotypes of STAT3 gain-of-function variant related to disruptive regulation of CXCL8/STAT3, KIT/STAT3, and IL-2/CD25/Treg axes.. Immunol Res (2021) 69:445–56.
    doi: 10.1007/s12026-021-09225-0pubmed: 34390446google scholar: lookup
  112. Beckman M, Srivastava SK, Lowder C, Baynes K, Sharma S. The use of Janus kinase inhibitors to treat noninfectious uveitis.. Invest Ophthalmol Vis Sci (2023) 64.
  113. Miserocchi E, Giuffrè C, Cornalba M, Pontikaki I, Cimaz R. JAK inhibitors in refractory juvenile idiopathic arthritis-associated uveitis.. Clin Rheumatol (2020) 39:847–51.
    doi: 10.1007/s10067-019-04875-wpubmed: 31897953google scholar: lookup
  114. Liu X-B, Tang L-S, Chen J-W, Lin C-S, Liu Q-H, Xu Q. Case report: A promising treatment strategy for noninfectious uveitis.. Front Pharmacol (2022) 12:784860.
    doi: 10.3389/fphar.2021.784860pmc: PMC8804343pubmed: 35115933google scholar: lookup
  115. Paley MA, Karacal H, Rao PK, Margolis TP, Miner JJ. Tofacitinib for refractory uveitis and scleritis.. Am J Ophthalmol Case Rep (2019) 13:53–5.
    doi: 10.1016/j.ajoc.2018.12.001pmc: PMC6288302pubmed: 30582071google scholar: lookup
  116. Bauermann P, Heiligenhaus A, Heinz C. Effect of janus kinase inhibitor treatment on anterior uveitis and associated macular edema in an adult patient with juvenile idiopathic arthritis.. Ocul Immunol Inflammation (2019) 27:1232–4.
    doi: 10.1080/09273948.2019.1605453pubmed: 31268748google scholar: lookup
  117. Álvarez-Reguera C, Prieto-Peña D, Herrero-Morant A, Sánchez-Bilbao L, Martín-Varillas JL, González-López E. Clinical and immunological study of Tofacitinib and Baricitinib in refractory Blau syndrome: case report and literature review.. Ther Adv Musculoskelet Dis (2022) 14.
    doi: 10.1177/1759720X221093211pmc: PMC9058350pubmed: 35510170google scholar: lookup
  118. Su Y, Tao T, Liu X, Su W. JAK-STAT signaling pathway in non-infectious uveitis.. Biochem Pharmacol (2022) 204:115236.
    doi: 10.1016/j.bcp.2022.115236pubmed: 36041544google scholar: lookup
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