CX3CR1+ Macrophages and CD8+ T Cells Control Intestinal IgA Production [MUCOSAL IMMUNOLOGY]

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.

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