title: 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 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.
authors.affiliation: Department of Immunology, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
authors.forename: Helen M
authors.initials: HM
authors.lastname: McGuire
authors.forename: Alexis
authors.initials: A
authors.lastname: Vogelzang
authors.forename: Cindy S
authors.initials: CS
authors.lastname: Ma
authors.forename: William E
authors.initials: WE
authors.lastname: Hughes
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Silveira
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
authors.forename: Daniel
authors.initials: D
authors.lastname: Christ
authors.forename: David
authors.initials: D
authors.lastname: Fulcher
authors.forename: Marika
authors.initials: M
authors.lastname: Falcone
authors.forename: Cecile
authors.initials: C
authors.lastname: King
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002465:Cell Movement; D002470:Cell Survival; D003920:Diabetes Mellitus / Q000276:immunology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054388:Receptors, CCR / Q000276:immunology*; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: C119309:CC chemokine receptor 9; D007378:Interleukins; D054388:Receptors, CCR; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21