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Home / Equine Research Bank / Osteoarthr Cartil Open / Regulatory T cells provide chondroprotection through increas...
Osteoarthritis and cartilage open2021; 3(3); 100193; doi: 10.1016/j.ocarto.2021.100193

Regulatory T cells provide chondroprotection through increased TIMP1, IL-10 and IL-4, but cannot mitigate the catabolic effects of IL-1β and IL-6 in a tri-culture model of osteoarthritis.

Abstract: To gain insight into Treg interactions with synovial tissues in early OA, an equine tri-culture model of OA was used to test the hypothesis that Tregs, in the absence of T Helper 17 ​cells, are sufficient to resolve inflammation elicited by IL-1β. Unassigned: To model normal and OA joints, synoviocytes were co-cultured with chondrocytes in a transwell system and ± stimulated with IL-1β. Tregs were activated and enriched, then added to co-cultures, creating tri-cultures. At culture end, synoviocytes and chondrocytes were analyzed for gene expression, Treg Foxp3 expression was reexamined by flow cytometry, and conditioned media were evaluated by ELISA. Unassigned: Tregs increased IL-10 and IL-4 in tri-culture media and increased gene expression in synoviocytes and chondrocytes. Tregs increased IL-6 in conditioned media and gene expression in synoviocytes, which was additive with IL-1β. In chondrocytes, addition of Tregs decreased gene expression while gene expression was decreased by IL-1β and addition of Tregs. IL-17A was detected in tri-cultures. CCL2 and CCL5 were increased in tri-cultures. Unassigned: In a tri-culture model of OA, addition of Tregs resulted in conditions conducive to chondroprotection including increased concentration of IL-10 and IL-4 in conditioned media and increased gene expression of in both chondrocytes and synoviocytes. However, there was increased concentration of the catabolic cytokine IL-6, and decreased gene expression of and in IL-1β-stimulated chondrocytes. These results suggest that blocking IL-6 could enhance Treg function in mitigating OA progression.
© 2021 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International (OARSI).
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Publication Date: 2021-07-16 PubMed ID: 36474817PubMed Central: PMC9718146DOI: 10.1016/j.ocarto.2021.100193Google 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 explores how regulatory T cells (Tregs) interact with synovial tissues in the early stages of osteoarthritis (OA) and their potential effect in mitigating OA progression.

Research Methods

  • The researchers used an equine tri-culture model of OA to test their hypothesis that Tregs, when affecting the system without T Helper 17 cells, can resolve inflammation caused by IL-1β.
  • The model attempted to replicate both normal and OA joints using synoviocytes, cells found in the synovial membrane of joints, and chondrocytes, the cells found in healthy cartilage.
  • These cells were stimulated with IL-1β and then Tregs, which had been enriched and activated, were added to the co-cultures creating tri-cultures.
  • At the end of the culture period, the team analyzed gene expression in the synoviocytes and chondrocytes, reexamined Treg Foxp3 expression by flow cytometry and assessed the conditioned media using an ELISA (Enzyme-Linked Immunosorbent Assay).

Findings

  • It was found that Tregs increased levels of IL-10 and IL-4 in tri-culture media and increased gene expression in synoviocytes and chondrocytes. These cytokines have been associated with anti-inflammatory responses in the body, indicating a potentially positive role by Tregs.
  • Tregs also increased the concentration of IL-6, another cytokine, in the conditioned media, and gene expression in synoviocytes. Interestingly, this effect was also seen with IL-1β, suggesting a complex interaction of these proteins.
  • Furthermore, the researchers observed an increased gene expression of molecules associated with inflammation – CCL2 and CCL5, when Tregs were present.
  • Lastly, while Tregs decreased specific gene expression in chondrocytes, they couldn’t suppress the gene expression decrease caused by the presence of IL-1β.

Conclusion

  • In conclusion, the research shows that when Tregs are added to a tri-culture model of osteoarthritis, conditions conducive to the protection of cartilage are created, which is presumably through the increased concentration of IL-10 and IL-4 and increased gene expression in both synoviocytes and chondrocytes.
  • However, Tregs also resulted in an increase in IL-6, a catabolic cytokine linked to tissue breakdown, and decreased gene expression in IL-1β-stimulated chondrocytes. This leads to the suggestion that blocking IL-6 could potentially enhance the effectiveness of Tregs in delaying or stopping the progression of osteoarthritis.

Cite This Article

APA
Keller LE, Tait Wojno ED, Begum L, Fortier LA. (2021). Regulatory T cells provide chondroprotection through increased TIMP1, IL-10 and IL-4, but cannot mitigate the catabolic effects of IL-1β and IL-6 in a tri-culture model of osteoarthritis. Osteoarthr Cartil Open, 3(3), 100193. https://doi.org/10.1016/j.ocarto.2021.100193

Publication

Osteoarthritis and cartilage open
ISSN: 2665-9131
NlmUniqueID: 101767068
Country: England
Language: English
Volume: 3
Issue: 3
Pages: 100193
PII: 100193

Researcher Affiliations

Keller, Laura E
  • Cornell University, College of Veterinary Medicine, Department of Clinical Sciences, USA.
Tait Wojno, Elia D
  • University of Washington, Department of Immunology, USA.
Begum, Laila
  • Cornell University, College of Veterinary Medicine, Department of Clinical Sciences, USA.
Fortier, Lisa A
  • Cornell University, College of Veterinary Medicine, Department of Clinical Sciences, USA.

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