title: Human TH9 cells are skin-tropic and have autocrine and paracrine proinflammatory capacity.
abstract: T helper type 9 (TH9) cells can mediate tumor immunity and participate in autoimmune and allergic inflammation in mice, but little is known about the TH9 cells that develop in vivo in humans. We isolated T cells from human blood and tissues and found that most memory TH9 cells were skin-tropic or skin-resident. Human TH9 cells coexpressed tumor necrosis factor-α and granzyme B and lacked coproduction of TH1/TH2/TH17 cytokines, and many were specific for Candida albicans. Interleukin-9 (IL-9) production was transient and preceded the up-regulation of other inflammatory cytokines. Blocking studies demonstrated that IL-9 was required for maximal production of interferon-γ, IL-9, IL-13, and IL-17 by skin-tropic T cells. IL-9-producing T cells were increased in the skin lesions of psoriasis, suggesting that these cells may contribute to human inflammatory skin disease. Our results indicate that human TH9 cells are a discrete T cell subset, many are tropic for the skin, and although they may function normally to protect against extracellular pathogens, aberrant activation of these cells may contribute to inflammatory diseases of the skin.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schlapbach
authors.forename: Ahmed
authors.initials: A
authors.lastname: Gehad
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.forename: Rei
authors.initials: R
authors.lastname: Watanabe
authors.forename: Emmanuella
authors.initials: E
authors.lastname: Guenova
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Teague
authors.forename: Laura
authors.initials: L
authors.lastname: Campbell
authors.forename: Nikhil
authors.initials: N
authors.lastname: Yawalkar
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Clark
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000276:immunology*; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D007376:Interleukin-2 / Q000494:pharmacology; D016906:Interleukin-9 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D019899:Paracrine Communication / Q000187:drug effects / Q000276:immunology*; D011565:Psoriasis / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D007376:Interleukin-2; D016906:Interleukin-9; D016212:Transforming Growth Factor beta