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Immunity. 2009 Sep 18;31(3):491-501. doi: 10.1016/j.immuni.2009.07.005. Epub 2009 Sep 3.

Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells.

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Immunology Section, BMC D14, Lund University, Lund 22184, Sweden.


T follicular helper (Tfh) cells represent a recently defined CD4(+) T cell subset characterized by the expression of the chemokine receptor CXCR5 and an enhanced ability to support B cells to mount antibody responses. Here, we demonstrate that lymph-node-resident CXCR5(+) Tfh cells and gut-homing integrin alpha(4)beta(7)-expressing T helper cells are generated as separate subsets in the gut-draining mesenteric lymph nodes. Type I interferon signaling in dendritic cells and in nonhematopoietic cells selectively stimulates Tfh cell development in response to antigen in conjunction with Toll-like receptor (TLR)3 or TLR4 agonists. Consistent with this, the ability of dendritic cells to produce the cytokine IL-6, required for in vivo Tfh differentiation, and antibody affinity maturation are both reduced in absence of type I interferon signaling. Thus, our results identify type I interferon as a natural adjuvant that selectively supports the generation of lymph node resident Tfh cells.

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