IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells

Marcel Batten, Nandhini Ramamoorthi, Noelyn M. Kljavin, Cindy S. Ma, Jennifer H. Cox, Hart S. Dengler, Dimitry M. Danilenko, Patrick Caplazi, Melanie Wong, David A. Fulcher, Matthew C. Cook, Cecile King, Stuart G. Tangye, Frederic J. De Sauvage, Nico Ghilardi*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    168 Citations (Scopus)

    Abstract

    Maturation and selection of high-affinity B cell clones in the germinal center (GC) relies on support from T follicular helper (TFH) cells. TFH cells are characterized by their localization to the B cell follicle and their high expression of the costimulatory molecules ICOS and PD1 and the cytokine IL-21, which promotes immunoglobulin (Ig) class switching and production by B cells. We show that the heterodimeric cytokine IL-27 is critical for the function of TFH cells and for normal and pathogenic GC responses. IL-27 signaling to T cells results in the production of IL-21, a known autocrine factor for the maintenance of TFH cells, in a STAT3-dependent manner. IL-27 also enhances the survival of activated CD4+ T cells and the expression of TFH cell phenotypic markers. In vivo, expression of the IL-27Rα chain is required to support IL-21 production and TFH cell survival in a T cell-intrinsic manner. The production of high-affinity antibodies is reduced, and pristane-elicited autoantibodies and glomerulonephritis are significantly diminished, in Il27ra-/- mice. Together, our data show a nonredundant role for IL-27 in the development of T cell-dependent antibody responses.

    Original languageEnglish
    Pages (from-to)2895-2906
    Number of pages12
    JournalJournal of Experimental Medicine
    Volume207
    Issue number13
    DOIs
    Publication statusPublished - 20 Dec 2010

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