Th17 cells, a class of CD4+ T cells, have been identified as novel effector cells, which play a pivotal role in several inflammatory and autoimmune diseases. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has emerged as a direct regulator of immune system function in humans. Accumulating reports demonstrated that 1,25(OH)2D3 possessed anti-inflammatory activity on Th17 cells to maintain immunologic homeostasis. This report will review the novel immune regulatory role of 1,25(OH)2D3 in its potential use for Th17 cell-related inflammatory and autoimmune conditions.
Expression of NK cell markers identifies pro-inflammatory T cell subsets in the liver and intestinal immune compartments. Specifically, CD161 is expressed on Th17 cells which play an important role in the regulation of mucosal inflammation. In this study, we characterized human peripheral blood CD161+ T cells as an effector population partially resembling a gut T cell phenotype. CD161+ CD4+ T cells express the gut-associated TNF family member, LIGHT, and respond to crosslinking of DR3, a receptor to another gut-associated cytokine, TL1A. Robust IFN-γ production in response to DR3 signaling correlated with enhanced expression of surface DR3 on CD161+ T cells and co-stimulation with IL12 and IL18. CD161+ T cell effector function was directly demonstrated by activation of responder monocytes in co-culture leading to CD40 upregulation and CD14 downregulation. CD161+ T cells reciprocally responded to activated monocytes, inducing expression of activation marker, CD69, and production of IL2 and IFN-γ, further demonstrating effective CD161+ T cell cross-talk with monocytes. Finally, CD161 defined a subset of T cells that co-express CD56, a second NK marker. Our findings implicate human CD161+ T cells in gut-associated signaling mechanisms, and suggest a monocyte mediated effector function in mucosal inflammation.