Journal
JOURNAL OF IMMUNOLOGY
Volume 201, Issue 4, Pages 1287-1294Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701459
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Funding
- National Research Foundation of Korea
- Ministry of Science, Information and Communications Technology and Future Planning [NRF-2017R1A2B4002419]
- Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute
- Ministry of Health and Welfare, Republic of Korea [HI15C1980]
- National Institutes of Health [AI113333, DK068181, DK091247, DK043351]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI081807, R01AI113333] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK068181, R01DK091247, P30DK043351] Funding Source: NIH RePORTER
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Secretory IgA is a key host defense mechanism that controls the intestinal microbiota. We investigated the role of CD11c(+)CX(3)CR1(+)CD64(+) macrophages in IgA production in the intestine. Intestinal CX(3)CR1(+) macrophages directly induced IgA secretion by B cells. Ag delivery to lamina propria (LP) CX(3)CR1(+) macrophages specifically induced intestinal IgA production. The induction of IgA by CX(3)CR1(+) macrophages required BAFF, a proliferation-inducing ligand, and TNF-alpha, but was surprisingly independent of TLR-mediated microbial recognition and retinoic acid signaling. IgA secretion by CX(3)CR1(+) macrophages was enhanced by LP CD8(+) T cells through the secretion of IL-9 and IL-13. CX(3)CR1(+) 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 CX(3)CR1(+) macrophages, B cells, and CD8(+) T cells coordinate the protective Ig secretion in the small intestine upon peripheral Ag delivery.
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