The cellular source and target of IL-21 in K/BxN autoimmune arthritis

Katharine E. Block, Haochu Huang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

IL-21 is a pluripotent cytokine that regulates B cell and plasma cell differentiation and is thought be an autocrine factor for follicular helper T cell (TFH) and Th17 differentiation. Although IL-21 has been implicated in autoimmune diseases, its relevant cellular source and target cells have not been well characterized. We investigated this issue in the K/BxN mouse model of autoimmune arthritis. Adoptive transfer of KRN-transgenic CD4+ T cells into appropriate hosts drives germinal center (GC) formation and autoantibody production against glucose-6-phosphate isomerase, leading to joint inflammation and destruction. By comparing transfer of T or B cells deficient in IL-21 or IL-21R, we were able to dissect the contribution of each cell type. T cells deficient in IL-21 did not induce GC formation or autoantibody production, but they went through normal TFH differentiation. However, T cells lacking IL-21R induced Ab titers, GC B cell frequency, and arthritis development similar to wild-type T cells, suggesting that IL-21 is not required for TFH differentiation and function. IL-21 acts on B cells, because IL-21R expression on B cells was required to induce disease. In contrast, Th17 cells, a T cell subset that also produces IL-21 and can provide help to B cells, are not required for the GC response and arthritis. These data have implications in developing effective therapies for rheumatoid arthritis and other Ab-mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)2948-2955
Number of pages8
JournalJournal of Immunology
Volume191
Issue number6
DOIs
StatePublished - Sep 15 2013
Externally publishedYes

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