Abstract
Alopecia areata (AA) is a chronic, relapsing hair-loss disorder that is considered to be a T-cell-mediated autoimmune disease. Several animal models for AA have been created to investigate the pathophysiology and screen for effective therapeutic targets. As C3H/HeJ mice develop AA spontaneously in a low frequency, a novel animal model is needed to establish an AA-like condition faster and more conveniently. In this study, we present a novel non-invasive AA rodent model that avoids skin or lymph-node cell transfer. We simply injected C3H/HeJ mice subcutaneously with interferon-gamma (IFNγ) along with polyinosinic:polycytidylic acid (poly[I:C]), a synthetic dsRNA, to initiate innate immunity via inflammasome activation. Approximately 80% of the IFNγ and poly(I:C) co-injected mice showed patchy AA lesions after 8 weeks. None of the mice displayed hair loss in the IFNγ or poly(I:C) solely injection group. Immunohistochemical staining of the AA lesions revealed increased infiltration of CD4+ and CD8+ cells infiltration around the hair follicles. IFNγ and poly(I:C) increased the expression of NLRP3, IL-1β, CXCL9, CXCL10, and CXCL11 in mouse skin. Taken together, these findings indicate a shorter and more convenient means of AA animal model induction and demonstrate that inflammasome-activated innate immunity is important in AA pathogenesis.
Highlights
Alopecia areata (AA) is a cell-mediated autoimmune disease that targets anagen-stage hair follicles
T cells and a collapse of immune privilege of hair follicle play a critical role in initiating AA and Janus kinase pathway, NKG2D and its ligands are identified as important factors in the pathogenesis of AA5,6 IFNγ is one of the key factors that lead to the collapse of immune privilege by upregulation of major histocompatibility complex in hair follicles and increase the occurrence rate of AA7,8
We found that affected mice showed lymphadenopathy with increased lymph node cell number and spleen weight (Fig. 1d–g). These results indicated that local injection of IFNγ and poly(I:C) lead to systemic inflammation, which is a well-known characteristic of an AA mouse model, in C3H/HeJ mice
Summary
Alopecia areata (AA) is a cell-mediated autoimmune disease that targets anagen-stage hair follicles. The most well-established animal models are inbred C3H/HeJ mice, which develop AA-like hair loss spontaneously or after experimental induction[3,4,5], as well as humanized mouse model with transplantations of human scalp skin followed by either autologous or allogenic peripheral blood mononuclear cells, to severe-combined immunodeficient (SCID) mice[6]. T cells and a collapse of immune privilege of hair follicle play a critical role in initiating AA and Janus kinase pathway, NKG2D and its ligands are identified as important factors in the pathogenesis of AA5,6 IFNγ is one of the key factors that lead to the collapse of immune privilege by upregulation of major histocompatibility complex in hair follicles and increase the occurrence rate of AA7,8. Recombinant murine interferon-gamma (IFNγ) along with poly(I:C) subcutaneously to trigger IL-1β-mediated inflammatory responses via the NF-κB pathway and inflammasome activation
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