A subset of interleukin-21(+) chemokine receptor CCR9(+) T helper cells target accessory organs of the digestive system in autoimmunity
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.|
|DOI||S1074-7613(11)00131-2 [pii] 10.1016/j.immuni.2011.01.021|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/21511186|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10727|