title: Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation.
abstract: Effector CD4+ T cell subsets, whose differentiation is facilitated by distinct cytokine cues, amplify the corresponding type of inflammatory response. Regulatory T (Treg) cells integrate environmental cues to suppress particular types of inflammation. In this regard, STAT3, a transcription factor essential for T helper 17 (Th17) cell differentiation, is necessary for Treg cell-mediated control of Th17 cell responses. Here, we showed that anti-inflammatory interleukin-10 (IL-10), and not proinflammatory IL-6 and IL-23 cytokine signaling, endowed Treg cells with the ability to suppress pathogenic Th17 cell responses. Ablation of the IL-10 receptor in Treg cells resulted in selective dysregulation of Th17 cell responses and colitis similar to that observed in mice harboring STAT3-deficient Treg cells. Thus, Treg cells limit Th17 cell inflammation by serving as principal amplifiers of negative regulatory circuits operating in immune effector cells.
authors.affiliation: Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chaudhry
authors.forename: Robert M
authors.initials: RM
authors.lastname: Samstein
authors.forename: Piper
authors.initials: P
authors.lastname: Treuting
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Liang
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Heinrich
authors.forename: Robert S
authors.initials: RS
authors.lastname: Jack
authors.forename: F Thomas
authors.initials: FT
authors.lastname: Wunderlich
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Rudensky
mesh_terms: D000818:Animals; D019070:Cell Lineage; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D053701:Receptors, Interleukin-10 / Q000172:deficiency / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D053701:Receptors, Interleukin-10; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10