Skin-infiltrating T cells and cytokine expression in Icelandic horses affected with insect bite hypersensitivity: a possible role for regulatory T cells.
Abstract: Equine insect bite hypersensitivity (IBH) is a seasonally recurrent, pruritic skin disorder caused by an IgE-mediated reaction to salivary proteins of biting flies, predominantly of the genus Culicoides. The aim of this study was to define T cell subsets and cytokine profile in the skin of IBH-affected Icelandic horses with particular focus on the balance between T helper (Th) 1, Th2 and T regulatory (Treg) cells. Distribution and number of CD4+, CD8+ and Forkhead box P3 (FoxP3)+ T cells were characterized by immunohistochemical staining in lesional and non-lesional skin of moderately and severely IBH-affected horses (n=14) and in the skin of healthy control horses (n=10). Using real-time quantitative reverse transcription-polymerase chain reaction, mRNA expression levels of Th2 cytokines (Interleukin (IL)-4, IL-5, IL-13), Th1 cytokines (Interferon-γ), regulatory cytokines (Transforming Growth Factor β1, IL-10) and the Treg transcription factor FoxP3 were measured in skin and blood samples. Furthermore, Culicoides nubeculosus specific serum IgE levels were assessed. Lesions of IBH-affected horses contained significantly higher numbers of CD4+ cells than skin of healthy control horses. Furthermore, the total number of T cells (CD4+ and CD8+) was significantly increased in lesional compared to non-lesional skin and there was a tendency (p=0.07) for higher numbers of CD4+ cells in lesional compared to non-lesional skin. While the number of FoxP3+ T cells did not differ significantly between the groups, the ratio of Foxp3 to CD4+ cells was significantly lower in lesions of severely IBH-affected horses than in moderately affected or control horses. Interestingly, differences in FoxP3 expression were more striking at the mRNA level. FoxP3 mRNA levels were significantly reduced in lesional skin, compared both to non-lesional and to healthy skin and were also significantly lower in non-lesional compared to healthy skin. Expression levels of IL-13, but not IL-4 or IL-5, were significantly elevated in lesional and non-lesional skin of IBH-affected horses. IL-10 levels were lower in lesional compared to non-lesional skin (p=0.06) and also lower (p=0.06) in the blood of IBH-affected than of healthy horses. No significant changes were observed regarding blood expression levels of Th1 and Th2 cytokines or FoxP3. Finally, IBH-affected horses had significantly higher Culicoides nubeculosus specific serum IgE levels than control horses. The presented data suggest that an imbalance between Th2 and Treg cells is a characteristic feature in IBH. Treatment strategies for IBH should thus aim at restoring the balance between Th2 and Treg cells.
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This study investigates the involvement of different types of T cells and cytokine protein profiles in the skin condition, insect bite hypersensitivity (IBH) in Icelandic horses. The research found imbalances in T helper cells and regulatory T cells in IBH-affected horses, suggesting potential therapeutic approaches based on restoring this balance.
Objective and Importance of the Study
The central aim of this study was to identify the types of T cells and their accompanying cytokine protein profiles in the skin of Icelandic horses affected by a skin disorder called insect bite hypersensitivity (IBH). This is an IgE-mediated reaction to salivary proteins from biting flies, especially in the genus Culicoides, that causes recurrent skin irritation.
The findings provide insight into the types and distribution of immune cells involved in IBH in horses, and they suggest potential new treatment strategies for restoring immune balance in affected animals.
Research Procedures and Findings
The researchers characterized the distribution and number of different T cell types (CD4+, CD8+ and FoxP3+) in the skin of both moderately and severely IBH-affected horses, and compared these with healthy control horses.
They found a significantly higher number of CD4+ cells in the skin lesions of horses with IBH compared to the skin of healthy horses. The total number of T cells (both CD4+ and CD8+) was also higher in lesioned skin compared to non-lesioned skin.
They went further to measure the expression levels of different types of cytokines (proteins that mediate and regulate immune and inflammatory responses), including Th2 cytokines (IL-4, IL-5, IL-13), Th1 cytokines (Interferon-γ), regulatory cytokines (Transforming Growth Factor β1, IL-10) and the Treg transcription factor FoxP3 in both skin and blood samples.
Although the number of FoxP3+ T cells did not differ significantly between the groups, a noticeable observation was that the ratio of FoxP3 to CD4+ cells was significantly lower in lesions from severely affected horses than in moderately affected or control animals.
IBH-affected horses also had significantly higher specific serum IgE levels against Culicoides nubeculosus than the control horses, indicating an immune response to this specific type of biting fly.
Implications for Future Treatment Strategies
The results of this research suggest that an imbalance between Th2 cells, which typically help to coordinate immune responses, and Treg cells, which help keep the immune system in check, is a key feature of IBH in horses.
Given this imbalance, the researchers suggested that future treatments for IBH should seek to restore balance between Th2 and Treg cells. This could potentially help alleviate symptoms of IBH and improve the horse’s quality of life.
Cite This Article
APA
Heimann M, Janda J, Sigurdardottir OG, Svansson V, Klukowska J, von Tscharner C, Doherr M, Broström H, Andersson LS, Einarsson S, Marti E, Torsteinsdottir S.
(2010).
Skin-infiltrating T cells and cytokine expression in Icelandic horses affected with insect bite hypersensitivity: a possible role for regulatory T cells.
Vet Immunol Immunopathol, 140(1-2), 63-74.
https://doi.org/10.1016/j.vetimm.2010.11.016
Lewis DH, Chan DL, Pinheiro D, Armitage-Chan E, Garden OA. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells. J Vet Intern Med 2012 May-Jun;26(3):457-82.