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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11c Antigen / immunology
  • Cell Differentiation*
  • Cell Lineage
  • Dendritic Cells / immunology*
  • Integrins / metabolism
  • Interferon Type I / immunology*
  • Interleukin-6 / biosynthesis
  • Lymph Nodes / cytology*
  • Lymph Nodes / immunology*
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Interferon alpha-beta / deficiency
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / immunology
  • Receptors, CXCR5 / metabolism
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • CD11c Antigen
  • CXCR5 protein, mouse
  • Ifnar1 protein, mouse
  • Integrins
  • Interferon Type I
  • Interleukin-6
  • Receptors, CXCR5
  • integrin alpha4beta7
  • Receptor, Interferon alpha-beta