Secretory IgA is a key host defense mechanism that controls the intestinal microbiota. We investigated the role of CD11c+CX3CR1+CD64+ macrophages in IgA production in the intestine. Intestinal CX3CR1+ macrophages directly induced IgA secretion by B cells. Ag delivery to lamina propria (LP) CX3CR1+ macrophages specifically induced intestinal IgA production. The induction of IgA by CX3CR1+ macrophages required BAFF, a proliferation-inducing ligand, and TNF-a, but was surprisingly independent of TLR-mediated microbial recognition and retinoic acid signaling. IgA secretion by CX3CR1+ macrophages was enhanced by LP CD8+ T cells through the secretion of IL-9 and IL-13. CX3CR1+ 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 CX3CR1+ macrophages, B cells, and CD8+ T cells coordinate the protective Ig secretion in the small intestine upon peripheral Ag delivery.
This work was supported by the National Research Foundation of Korea; the Ministry of Science, Information and Communications Technology and Future Planning (NRF-2017R1A2B4002419); a grant from the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute;and by the Ministry of Health and Welfare, Republic of Korea (Grant HI15C1980). H.-C.R. was supported by National Institutes of Health Grants AI113333, DK068181, DK091247, and DK043351.
