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J Immunol. 2018 Aug 15;201(4):1287-1294. doi: 10.4049/jimmunol.1701459. Epub 2018 Jul 9.

CX3CR1+ Macrophages and CD8+ T Cells Control Intestinal IgA Production.

Author information

1
Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon 16499, Korea.
2
Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Korea.
3
Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
4
Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
5
Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05535, Korea.
6
Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul 08826, Korea; and.
7
Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Gwanak-gu, Seoul 08826, Korea.
8
Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; sychang@ajou.ac.kr hans-christian_reinecker@hms.harvard.edu.
9
Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon 16499, Korea; sychang@ajou.ac.kr hans-christian_reinecker@hms.harvard.edu.

Abstract

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-α, 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.

PMID:
29987162
PMCID:
PMC6082403
[Available on 2019-08-15]
DOI:
10.4049/jimmunol.1701459
[Indexed for MEDLINE]

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