TY - JOUR
T1 - Interleukin-10 Signaling in Regulatory T Cells Is Required for Suppression of Th17 Cell-Mediated Inflammation
AU - Chaudhry, Ashutosh
AU - Samstein, Robert M.
AU - Treuting, Piper
AU - Liang, Yuqiong
AU - Pils, Marina C.
AU - Heinrich, Jan Michael
AU - Jack, Robert S.
AU - Wunderlich, F. Thomas
AU - Brüning, Jens C.
AU - Müller, Werner
AU - Rudensky, Alexander Y.
N1 - Funding Information:
We would like to thank A. Bravo, J. Herlihy, J. Gerard, and P. Zarin for help with the mouse colony management; H. Lee for superb technical assistance; J.-C. Renauld for anti-IL-22; V. Kuchroo for Il23r −/− mice; and D. Schenten, S. Nish, and R. Medzhitov for help in facilitating key experiments. The generation of the conditional IL-10R1 mouse mutant was supported by the DFG, Sonderforschungsbereich 621, Project A2, and the European Union Grant MUGEN LSHG-CT-2005-005203. This work was supported by grants from the National Institutes of Health (A.Y.R.). A.C. is supported by the Irvington Institute Fellowship Program of the Cancer Research Institute. R.M.S. was supported by NIH MSTP grant GM07739. A.Y.R. is an investigator with the Howard Hughes Medical Institute.
PY - 2011/4/22
Y1 - 2011/4/22
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/79954608612
U2 - 10.1016/j.immuni.2011.03.018
DO - 10.1016/j.immuni.2011.03.018
M3 - Article
C2 - 21511185
AN - SCOPUS:79954608612
SN - 1074-7613
VL - 34
SP - 566
EP - 578
JO - Immunity
JF - Immunity
IS - 4
ER -