An unexpected twist in alopecia areata pathogenesis: are NK cells protective and CD49b+ T cells pathogenic?

Abstract

Natural killer (NK) cells have become a recent focus of interest in alopecia areata (AA) research. To further investigate their role in an established mouse model of AA, lesional skin from older C3H ⁄ HeJ mice with AA was grafted to young C3H ⁄ HeJ female mice, and NK cells were depleted by continuous administration of rabbit anti-asialo GM1. As expected, this significantly reduced the number of pure NK cells in murine skin, as assessed by NKp46 quantitative immunohistochemistry. Quite unexpectedly, however, the onset of hair loss in C3H ⁄ HeJ mice was accelerated, rather than retarded. NK cell depletion was accompanied by a significant increase in the number of perifollicular CD49b+T cells in the alopecic skin of anti-asialo GM1-treated mice. These findings underscore the need to carefully distinguish in future AA research between pure NK cells and defined subsets of CD49b+ lymphocytes, as they may exert diametrically opposed functions in hair follicle immunology and immunopathology.

Environmental stress but not subjective distress in children or adolescents with alopecia areata

“…The sympathetic nervous system activity has been linked to an increased NK cell activity [40], in coincidence with our trend observation of higher counts of NK cells in both of our patient groups. Nevertheless, the role of NK cells in autoimmune disorders remains controversial [21], as NK-cell depletion has been shown to both diminish [41] and increase [42] the clinical symptoms of autoimmune disease. The role of NK cells could be proinflammatory [19].…”

“…IgA levels can be used as an indicator of acute stress since they are more sensitive to social stress than the levels of cortisol [16]. Lymphocyte count and proportion of natural killer (NK) cells variations have been observed to be associated with alexithymia [17] and with AA [18], and there is renewed interest on the implication of the NK cells in the pathogenesis of autoimmune diseases including AA [19,20,21].…”

Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

“…Since AA is a T-cell-mediated, organ-specific autoimmune disease, 125 it offers an excellent model for probing the functional relationship between autoreactive T cells and the putative HF IP. AA also promises pointers to the functional relevance of HF IP.…”

Hair follicle is a target of stress hormone and autoimmune reactions

“…In this murine model, unexpectedly, the onset of hair loss in C3H/ HeJ mice was accelerated with NK-cell depletion by continuous administration of rabbit anti-asialo GM1. The NK-cell depletion was accompanied by a significant increase in the number of perifollicular CD49b+ T cells in the alopecic skin of anti-asialo GM1-treated mice [52]. Careful studies of the roles of pure NK cells in the pathogenesis of AA are further needed.…”