IFN-γ, IL-21, and IL-10 Co-Expression in Evolving Autoimmune Vitiligo Lesions of Smyth Line Chickens

Abstract

The Smyth line (SL) of chicken is an excellent animal model for human autoimmune vitiligo. In SL vitiligo (SLV) post-natal loss of melanocytes in feathers appears to be due to cell-mediated immunity. In this study, leukocyte-infiltration and associated expression (RNA) of immune function-related cytokines in growing feathers were investigated throughout SLV-development and -progression. Both leukocyte infiltration and cytokine expression levels started to increase near visible SLV onset (early SLV), reached peak levels during active SLV, and decreased to near pre-vitiligo levels after complete loss of melanocytes. Specifically, significant increases were noticed in relative proportions of T cells, B cells, and MHC II-expressing cells during active SLV. Levels of T cell infiltration were higher than those of B cells, with more CD8+ than CD4+ cells throughout SLV. Elevated leukocyte infiltration in early and active SLV was accompanied by increased levels of cytokine expression, especially in interferon-gamma, interleukin (IL)-10 and IL-21. Low expression of IL-4 and IL-17 did not suggest important roles of Th2 and Th17 cells in SLV pathogenesis. Taken together, SLV appears to be a Th1 polarized autoimmune disease, whereby interferon-gamma expression is strongly associated with parallel increases in IL-10 and IL-21, particularly during early and active stages of SLV.

Understanding mechanisms of vitiligo development in Smyth line of chickens by transcriptomic microarray analysis of evolving autoimmune lesions

“…inflammatory response and immunological disease) (Figure 1 and 2). DE genes of both T and B cell markers (Table 1 and 2) and functions of humoral and cell-mediated immune response (Figure 1 and 2) in the current study are in line with previous studies demonstrating involvement of both types of immune responses in melanocyte loss in the etiology of SLV [6,10,12,16]. Furthermore, it appears that the humoral immune response was particularly important in early SLV development, since DE genes in EV samples were significantly (1 st network) associated with this function (Figure 2).…”

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

“…Studies of Smyth line chickens, an animal model for human autoimmune vitiligo, have demonstrated that elevated leukocyte infiltration in early and active vitiligo is accompanied by increased levels of cytokine expression, especially in interferon (IFN)-IL-10, and IL-21 [68]. Recently, in a mouse model of spontaneous melanoma, Treg cell-depletion and IL-10 neutralisation led to an increased occurrence of vitiligo which correlated with a decreased incidence of melanoma metastases [69].…”

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes <i>via</i> Inhibition of JAK2: Its Implication for Vitiligo Treatment

“…4,18,19) In vitiligo patients and animal models, IFN-γ level is significantly elevated in lesional skin. 4,20) IFN-γ signaling regulates the expression of cytokine as well as adhesion molecules facilitating the lymphocyte migration. 16,21) So that, local IFN-γ release promotes further recruitment of melanocyte-specific CD8+ T cells into the vitiligo lesion.…”