title: Th17 cells express interleukin-10 receptor and are controlled by Foxp3⁻ and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner.
abstract: T helper 17 (Th17) cells are important for host defense against extracellular microorganisms. However, they are also implicated in autoimmune and chronic inflammatory diseases, and as such need to be tightly regulated. The mechanisms that directly control committed pathogenic Th17 cells in vivo remain unclear. We showed here that IL-17A-producing CD4+ T cells expressed interleukin-10 receptor α (IL-10Rα) in vivo. Importantly, T cell-specific blockade of IL-10 signaling led to a selective increase of IL-17A+IFN-γ⁻ (Th17) and IL-17A+IFN-γ+ (Th17+Th1) CD4+ T cells during intestinal inflammation in the small intestine. CD4+Foxp3⁻ IL-10-producing (Tr1) cells and CD4+Foxp3+ regulatory (Treg) cells were able to control Th17 and Th17+Th1 cells in an IL-10-dependent manner in vivo. Lastly, IL-10 treatment of mice with established colitis decreased Th17 and Th17+Th1 cell frequencies via direct signaling in T cells. Thus, IL-10 signaling directly suppresses Th17 and Th17+Th1 cells.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.forename: Nicola
authors.initials: N
authors.lastname: Gagliani
authors.forename: Enric
authors.initials: E
authors.lastname: Esplugues
authors.forename: William
authors.initials: W
authors.lastname: O'Connor
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Huber
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Masahito
authors.initials: M
authors.lastname: Kamanaka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Booth
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Manuela
authors.initials: M
authors.lastname: Battaglia
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D003092:Colitis / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D053709:Interleukin-10 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D015398:Signal Transduction; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D053709:Interleukin-10 Receptor alpha Subunit; D010446:Peptide Fragments; C069261:interferon gamma (1-39); D016753:Interleukin-10; D007371:Interferon-gamma