A Subset of Interleukin-21+ Chemokine Receptor CCR9+ T Helper Cells Target Accessory Organs of the Digestive System in Autoimmunity

Helen M. McGuire, Alexis Vogelzang, Cindy S. Ma, William E. Hughes, Pablo A. Silveira, Stuart G. Tangye, Daniel Christ, David Fulcher, Marika Falcone, Cecile King

Research output: Contribution to journalArticle

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 Sjögren'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.

Original languageEnglish
Pages (from-to)602-615
Number of pages14
JournalImmunity
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 22 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    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. (2011). A Subset of Interleukin-21+ Chemokine Receptor CCR9+ T Helper Cells Target Accessory Organs of the Digestive System in Autoimmunity. Immunity, 34(4), 602-615. https://doi.org/10.1016/j.immuni.2011.01.021