043 Regulatory natural killer cells in alopecia areata

Abstract

Alopecia areata (AA) is a T-cell mediated autoimmune disease of hair follicle. Although the polymorphisms in the ULBP3/6 ligands of activating receptor NKG2D has been shown to associate with AA, the role of natural killer (NK) cells in AA is not fully defined. NK cells are major components of innate immunity and play critical roles in early defense against microbial pathogens and tumors. Recent reports indicate that NK cells play opposite roles with both pathogenic and regulatory activity in some autoimmune disorders. The protective role of NK cells was previously reported in C3H/HeJ mouse model of AA, however, little is known about the mechanisms of this protective function. Here we also found that NK cell depletion accelerates the development of AA in C3H/HeJ mice. Murine NK cells can be divided into distinct subsets based on the expression of Mac-1 and CD27. Mac-1high CD27high NK cells exhibit higher cytotoxicity against target cells than other NK cell subsets. We detected a higher percentage of Mac-1high CD27high NK cells in skin draining lymph nodes from new-onset AA mice (after grafting) than from control C3H/HeJ mice without AA. The expression of CD69, LAG-3, KLRG1 and TIGIT was also significantly increased on this population of NK cells in AA mice, indicative of activation of these NK cells in AA. It has been suggested that NK cells may homeostatically control inflammation by targeting activated T cells via engagement of NK activating receptors by T cell expression of NKG2DLs, Qa-1 and/or through LFA-1/ICAM-1 interactions. We detected higher levels of ICAM-1 on activated CD4 and CD8 T cells than on their naïve counterparts, which could render activated T cells vulnerable to NK-mediated cytolysis. Our data suggests that Mac-1high CD27high NK cells may inhibit autoimmune T cell responses by regulating activated autoantigen-specific T cells.