Key role for IL-21 in experimental autoimmune uveitis

Abstract

IL-21 is a pleiotropic type 1 cytokine that shares the common cytokine receptor γ-chain, γ c , with IL-2, IL-4, IL-7, IL-9, and IL-15. IL-21 is most homologous to IL-2. These cytokines are encoded by adjacent genes, but they are functionally distinct. Whereas IL-2 promotes development of regulatory T cells and confers protection from autoimmune disease, IL-21 promotes differentiation of Th17 cells and is implicated in several autoimmune diseases, including type 1 diabetes and systemic lupus erythematosus. However, the roles of IL-21 and IL-2 in CNS autoimmune diseases such as multiple sclerosis and uveitis have been controversial. Here, we generated Il21 -mCherry/ Il2 -emGFP dual-reporter transgenic mice and showed that development of experimental autoimmune uveitis (EAU) correlated with the presence of T cells coexpressing IL-21 and IL-2 into the retina. Furthermore, Il21r −/− mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r −/− T cells induced much less severe EAU, underscoring the need for IL-21 in the development of this disease and suggesting that blocking IL-21/γ c –signaling pathways may provide a means for controlling CNS auto-inflammatory diseases.

T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite

“…To further confirm this conclusion, we used Il21 -mCherry and Il2 -emGFP BAC dual reporter Tg mice (Wang et al, 2011). Analysis of mLNs of dual reporter BM chimeric mice on day 6 after HDM sensitization identified a population of CD44 hi CD4 + T cells that were Il21 -mCherry + Il2 -emGFP − (mCherry-IL-21 + ) (Figure 6A).…”

Gestational and lactational exposure to low-dose bisphenol A increases Th17 cells in mice offspring

“…IL-21 is a member of IL-2 family cytokines and is produced mainly by Th17 cells. IL-21 can positively regulate Th17 cells and stimulates non-immune cells to produce inflammatory mediators, thus facilitating autoimmune diseases (Wang et al, 2011). It has been shown that IL-21 can substitute for IL-6 to promote Th17 cell differentiation (Korn et al, 2007;Nurieva et al, 2007).…”

Dynamic Long-Range Chromatin Interaction Controls Expression of IL-21 in CD4+ T Cells

“…Elevated expression of IL-21 was observed in NOD mice (12), and blocking IL-21 signaling leads to the abrogation of disease development (13). IL-21 also plays a role in the development of B cell-mediated autoimmune disease (7), experimental allergic encephalitis (14), experimental autoimmune uveitis (15), and the epidermal hyperplasia of psoriasis (16). Additionally, genome-wide association studies revealed that the IL21 locus is implicated in celiac disease and alopecia areata (17,18).…”