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A subset of interleukin-21(+) chemokine receptor CCR9(+) T helper cells target accessory organs of the digestive system in autoimmunity

Abstract

This study describes a CD4(+) T helper (Th) cell subset marked by coexpression of the cytokine interleukin 21 (IL-21) and the gut-homing chemokine receptor CCR9. Although CCR9(+) Th cells were observed in healthy mice and humans, they were enriched in the inflamed pancreas and salivary glands of NOD mice and in the circulation of Sjogren's syndrome patients. CCR9(+) Th cells expressed large amounts of IL-21, inducible T cell costimulator (ICOS), and the transcription factors Bcl6 and Maf, and also supported antibody production from B cells, thereby resembling T follicular B helper (Tfh) cells. However, in contrast to Tfh cells, CCR9(+) Th cells displayed limited expression of CXCR5 and the targets of CCR9(+) Th cells were CD8(+) T cells whose responsiveness to IL-21 was necessary for the development of diabetes. Thus, CCR9(+) Th cells are a subset of IL-21-producing T helper cells that influence regional specification of autoimmune diseases that affect accessory organs of the digestive system.

ISBN 1097-4180 (Electronic) 1074-7613 (Linking)
Authors McGuire, H. M.; Vogelzang, A.; Ma, C. S.; Hughes, W. E.; Silveira, P. A.; Tangye, S. G.; Christ, D.; Fulcher, D.; Falcone, M.; King, C., C.
Garvan Authors A/Prof Cecile King , Dr William Hughes
Publisher Name IMMUNITY
Published Date 2011-04-21 00:00:00
Published Volume 34
Published Issue 4
Published Pages 602-15
URL http://www.ncbi.nlm.nih.gov/pubmed/21511186
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?10727_11386/11 McGuire Immunity_.pdf