BLT1 mediates commensal bacteria-dependent innate immune signals to enhance antigen-specific intestinal IgA responses

BLT1 介导共生菌依赖性先天免疫信号,增强抗原特异性肠道 IgA 反应

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作者:Takahiro Nagatake, So-Ichiro Hirata, Tomoaki Koga, Etsushi Kuroda, Shingo Kobari, Hidehiko Suzuki, Koji Hosomi, Naomi Matsumoto, Yaulia Yanrismet, Michiko Shimojou, Sakiko Morimoto, Fumiyuki Sasaki, Ken J Ishii, Takehiko Yokomizo, Jun Kunisawa

Abstract

Leukotriene B4 receptor 1 (BLT1) triggers the migration of granulocytes and activated T cells; however, its role in B-cell function remains unclear. Here we report that BLT1 is required to induce the production of antigen-specific IgA against oral vaccine through mediating innate immune signals from commensal bacteria. B cells acquire BLT1 expression during their differentiation to IgA+ B cells and plasma cells in Peyer's patches and the small intestinal lamina propria, respectively. BLT1 KO mice exhibited impaired production of antigen-specific fecal IgA to oral vaccine despite normal IgG responses to systemically immunized antigen. Expression of MyD88 was decreased in BLT1 KO gut B cells and consequently led to diminished proliferation of commensal bacteria-dependent plasma cells. These results indicate that BLT1 enhances the proliferation of commensal bacteria-dependent IgA+ plasma cells through the induction of MyD88 and thereby plays a key role in the production of antigen-specific intestinal IgA.

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