Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells.
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.
Cucak
Helena
H
Immunology Section, BMC D14, Lund University, Lund 22184, Sweden.
Yrlid
Ulf
U
Reizis
Boris
B
Kalinke
Ulrich
U
Johansson-Lindbom
Bengt
B
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000276:immunology*; D016023:Integrins / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D054380:Receptors, CXCR5 / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D039521:CD11c Antigen; C513179:CXCR5 protein, mouse; C508032:Ifnar1 protein, mouse; D016023:Integrins; D007370:Interferon Type I; D015850:Interleukin-6; D054380:Receptors, CXCR5; C071777:integrin alpha4beta7; D053633:Receptor, Interferon alpha-beta