Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon 16499, Korea.
Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Korea.
J Immunol. 2018 Aug 15;201(4):1287-1294. doi: 10.4049/jimmunol.1701459. Epub 2018 Jul 9.
Secretory IgA is a key host defense mechanism that controls the intestinal microbiota. We investigated the role of CD11cCXCR1CD64 macrophages in IgA production in the intestine. Intestinal CXCR1 macrophages directly induced IgA secretion by B cells. Ag delivery to lamina propria (LP) CXCR1 macrophages specifically induced intestinal IgA production. The induction of IgA by CXCR1 macrophages required BAFF, a proliferation-inducing ligand, and TNF-α, but was surprisingly independent of TLR-mediated microbial recognition and retinoic acid signaling. IgA secretion by CXCR1 macrophages was enhanced by LP CD8 T cells through the secretion of IL-9 and IL-13. CXCR1 macrophages and CD8 T cells induced IgA production by B cells independently of mesenteric lymph nodes and Peyer patches. Our data reveal a previously unrecognized cellular circuitry in which LP CXCR1 macrophages, B cells, and CD8 T cells coordinate the protective Ig secretion in the small intestine upon peripheral Ag delivery.
分泌型免疫球蛋白 A（Secretory IgA）是一种控制肠道微生物群的关键宿主防御机制。我们研究了 CD11cCXCR1CD64 巨噬细胞在肠道中 IgA 产生中的作用。肠道 CXCR1 巨噬细胞直接诱导 B 细胞分泌 IgA。Ag 递送至固有层（LP）CXCR1 巨噬细胞可特异性诱导肠道 IgA 产生。CXCR1 巨噬细胞诱导 IgA 需要 BAFF（增殖诱导配体）和 TNF-α，但令人惊讶的是，这一过程独立于 TLR 介导的微生物识别和视黄酸信号通路。LP CD8 T 细胞通过分泌 IL-9 和 IL-13 增强了 CXCR1 巨噬细胞的 IgA 分泌。CXCR1 巨噬细胞和 CD8 T 细胞通过 B 细胞独立于肠系膜淋巴结和派尔集合淋巴结诱导 IgA 产生。我们的数据揭示了一个以前未被认识的细胞电路，其中 LP CXCR1 巨噬细胞、B 细胞和 CD8 T 细胞在外周 Ag 递送至肠道时协调保护性 IgA 的分泌。
