Plasmacytoid dendritic cells as a key player in the initiation phase of alopecia areata-induced C3H/HeJ mouse

Abstract

Recently, the pathomechanism of alopecia areata (AA) has been thought to be a tissue-specific autoimmune disease. So far, interferon (IFN)-γ has been regarded as the most important key cytokine that may induce the collapse of HF immune privilege, apotosis and the upregulation of CXCL 10 in C3H/HeJ AA mouse. In this study, we focus on the role of type I IFN, IFN-α, in the initiation of AA. We previously reported seven cases of AA, including both new onset and recurrent AA, following swine flu viral infection. In this study, we generate AA-induced C3H/HeJ mouse by intra-dermal injection of activated lymphonode cells with IL-2, IL-7 and IL-15. Immunohistochemical staining revealed that IFN-α producing plasmacytoid dendritic cells (pDCs) densely distributed around HFs in not only lesion skin but also non-lesional skin obtained from AA induced-C3H/HeJ mice. Flowcytometric analysis showed the increased frequency of pDCs in skin-infiltrated cells of non-lesional skin from C3H/HeJ mice with AA. Real-time PCR also showed higher expression of IFN-α2, IFN-α4 and chemerin mRNA in C3H/HeJ mouse with AA. In vitro study, IFN-α inhibited the hair elongation of cultured murine vibrissae in Willium's E medium by Philpott's model. In addition, H-2k and CXCL10 expression were upregulated in cultured murine vibrissae by IFN-α. Imiquimod (IMQ) is the potent inducer of IFN-α via TLR7/9 on pDCs. IMQ applied C3H/HeJ mouse showed retardation of hair cycle stage compared to control mouse with infiltration of SiglecH + pDCs with IFN-α expression by immunohistochemical staining. Finally, we succeeded the induction of AA only by intra-dermal injection of pDCs in C3H/HeJ mouse. In conclusion, pDCs may play an important role for the initiation of AA by over expression of IFN-α via pDCs.