Melanocyte-specific cell mediated immune response in vitiliginous Smyth line chickens

Apoptosis in feathers of Smyth line chickens with autoimmune vitiligo

“…Although several studies have shown quantitative abnormalities of NK cells in the peripheral blood of vitiligo patients [40,41], NK cells have not been localized in lesional or perilesional areas of vitiliginous skin [42]. In contrast, an important role of CTLmediated cytotoxicity in the destruction of MCs in human and SL vitiligo has been strongly suggested [25,27,43]. Here, we further demonstrate a link between CD8+ cells and apoptosis at the site of MC loss.…”

“…In SLV and human vitiligo, an intrinsic MC defect may contribute to the induction of apoptosis. An inherent MC defect in SL chickens was suggested by the abnormal appearance of melanosomes and the endoplasmic reticulum in SL MCs, the autophagocytosis of melanosomes in SL MCs, retraction of MC dendrites prior to the visible onset of SLV [47,48] and a lower survival rate of SL MC than BL MC in establishment of MC cultures [27]. The mechanisms by which an inherent MC defect may contribute to MC apoptosis need to be defined.…”

“…The cross-reactivity of this mAb with chicken MCs was established in a variety of ways, including binding of the mAb to cultured chicken embryo-derived and feather-derived MCs and to feather MCs in normally pigmented feather sections. Moreover, M2-7C10 was found to recognize a similar size protein in chicken MC lysates as in human MC lysates, but did not interact with proteins in a cell lysate prepared from chicken-embryo fibroblasts [27].…”

“…Like in humans, an important role of CMI in the destruction of MC in SLV has been suggested by previous studies. Evidence supporting CMI as an effector mechanism in SLV includes the following observations: the loss of MC in feathers of SL chickens is always associated with large numbers of feather infiltrating lymphocytes composed predominantly of CD4+ and CD8+ T cells [25,26]; the ratio between feather infiltrating CD4+ cells and CD8+ cells, which was about 1.2 at visible onset of vitiligo, dropped to near 0.3 as a result of an increase in CD8+ cells during the progression of vitiligo [25,26]; and, vitiliginous SL chickens exhibit an in vivo CMI response to MHC-matched feather MC lysates [27]. These observations, together with a noted absence of inflammatory cells in the feather, suggest a role of cytotoxic T cellmediated mechanisms in MC death.…”

Immunodetection of the MCHR1 antibody in vitiligo patient sera

“…One of the most popular hypotheses considers vitiligo as an autoimmune disease. Previous investigations have proven that the anti-melanocyte antibody, which destroys the skin melanocyte, is one of the important autoantibodies causing vitiligo (11)(12)(13). The important antigens detected in vitiligo patients include, but may not be limited to, tyrosinase (5), tyrosinase-related protein-1 (TRP-1) (7), tyrosinaserelated protein-2 (TRP-2) (6), Pmel17 (14), the transcription factor SOX10 (8) and MCHR1 (9).…”