Interleukin-10 Signaling in Regulatory T Cells Is Required for Suppression of Th17 Cell-Mediated Inflammation

Ashutosh Chaudhry, Robert M. Samstein, Piper Treuting, Yuqiong Liang, Marina C. Pils, Jan Michael Heinrich, Robert S. Jack, F. Thomas Wunderlich, Jens C. Brüning, Werner Müller, Alexander Y. Rudensky

    Research output: Contribution to journalArticlepeer-review

    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. © 2011 Elsevier Inc.
    Original languageEnglish
    Pages (from-to)566-578
    Number of pages12
    JournalImmunity
    Volume34
    Issue number4
    DOIs
    Publication statusPublished - 22 Apr 2011

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