Decreased expression levels of complement regulator CD55 contribute to the development of bullous pemphigoid
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Pei Qiao1,*, Er-Le Dang1,*, Hui Fang1, Jie-Yu Zhang1, Bing Li1, Sheng-Xian Shen1, Yi-Xin Luo1, Jie Lei1, Shuai Shao1, Hong-Jiang Qiao1 and Gang Wang1
1Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province, China
*These authors have contributed equally to this work
Gang Wang, email: [email protected]
Keywords: bullous pemphigoid, complement, CD55, ERK1/2, autoimmunity
Received: June 23, 2017 Accepted: August 27, 2017 Epub: September 23, 2017 Published: October 30, 2018
Bullous pemphigoid is a common autoimmune blistering disease of the elderly associated with autoantibody-mediated complement activation, and complement dysregulation is critical for its pathogenesis. As a crucial regulator of the complement system, CD55 has been widely studied in autoimmune diseases. Here, we investigated the involvement of CD55 in bullous pemphigoid, as little is known regarding its role in this disease. We found that CD55 levels were significantly lower in the lesions of patients with bullous pemphigoid (n = 8) compared to those in skin samples from healthy controls (n = 6). Interestingly, CD55 depletion in HaCaT human keratinocytes enhanced autoantibody-mediated complement activation. Moreover, complement activation was blocked by exogenous recombinant CD55 protein in both skin sections and keratinocytes exposed to pathogenic antibodies from patients with bullous pemphigoid. Notably, a significant increase in the expression of TNF-α and IFN-γ, administration of which downregulated CD55 levels in HaCaT cells, was observed in the sera of patients with bullous pemphigoid (n = 38) compared to that in healthy controls (n = 19). We found that ERK1/2 is involved in both TNF-α- and IFN-γ-induced CD55 downregulation. Thus, CD55 deficiency is a crucial factor in bullous pemphigoid pathogenesis, suggesting that increasing CD55 levels may exert a therapeutic effect.
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