IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells
Date
2010
Authors
Batten, Marcel L
Ramamoorthi, Nandhini
Kljavin, Noelyn M
Ma, Cindy
Cox, Jennifer H
Dengler, Hart S
Danilenko, Dimitry M
Caplazi, Patrick
Wong, Melanie
Fulcher, David
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Rockefeller University Press
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.
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Keywords: autoantibody; interleukin 21; interleukin 27; interleukin 27 receptor alpha; interleukin receptor; pristane; STAT3 protein; unclassified drug; animal cell; animal experiment; animal model; animal tissue; antibody production; article; cell function; cell s
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Journal of Experimental Medicine
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Journal article
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2037-12-31
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