title: IL-9(+) IL-10(+) T cells link immediate allergic response to late phase reaction.
abstract: The mechanism underlying late-phase allergic reactions (LPR) remains incompletely understood. This study aimed to investigate the role of a newly described subset of T cells, interleukin (IL)-9(+) IL-10(+) T cells, in the pathogenesis of LPR. Using a T helper type 2 (Th2) inflammatory mouse model, we examined the frequency of IL-9(+) IL-10(+) T cells in the jejunum by immunohistochemistry. The LPR in the jejunum was observed afterwards. The cytokine profile of IL-9(+) IL-10(+) T cells was characterized and the major cytokine that plays the critical role in the initiation of LPR was investigated. Abundant IL-9(+) IL-10(+) T cells as well as inflammatory cell extravasation in the jejunal sections were observed in sensitized mice 48 h after specific antigen challenge. IL-9(+) IL-10(+) T cells expressed high levels of macrophage inflammatory protein 1 (MIP1) that could be enhanced by T cell receptor activation. MIP1 facilitated macrophage extravasation in local tissue. Macrophage-derived MIP2 contributed to neutrophil infiltration in the intestine in LPR. Pretreatment with anti-MIP antibody inhibited the LPR in the intestine. IL-9(+) IL-10(+) T cells play an important role in LPR. This subset of T cells has the potential to be a novel therapeutic target in the treatment of LPR and LPR-related inflammation.
authors.affiliation: Clinical Experimenmtal Center, The First Affiliated Hospital, Nanjing Medical University, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: S-H
authors.initials: SH
authors.lastname: He
authors.forename: Z-Q
authors.initials: ZQ
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: C-H
authors.initials: CH
authors.lastname: Song
authors.forename: L-F
authors.initials: LF
authors.lastname: Zhou
authors.forename: W-J
authors.initials: WJ
authors.lastname: Ma
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: Y
authors.initials: Y
authors.lastname: Du
authors.forename: S-G
authors.initials: SG
authors.lastname: Tang
authors.forename: P-C
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007114:Immunization; D016753:Interleukin-10 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis; D007583:Jejunum / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D054405:Chemokine CCL3; D016906:Interleukin-9; D016753:Interleukin-10