IL‐33‐activated murine mast cells control the dichotomy between RORγt+ and Helios+Tregs via the MK2/3‐mediated IL‐6 production in vitro. Issue 12 (30th July 2019)

• Record Type: Journal Article
• Authors: Andreas, Nico; Weber, Franziska; Meininger, Isabel; Templin, Nicole; Gaestel, Matthias; Kamradt, Thomas; Drube, Sebastian
• Is Part Of: European journal of immunology. Volume 49:Issue 12(2019)
• Page Start: 2159
• Page End: 2171
• Publication Date: 2019-07-30
• Subjects: IL‐33 -- IL‐6 -- Mast cells -- Tregs -- MK2/3; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948154
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: In mast cells, IL‐33 typically induces the activation of NF‐κB, which results in the production of cytokines such as IL‐6 and IL‐2. Here, we demonstrate that the IL‐33‐induced IL‐6 production in murine mast cells and the formation of RORγt + T regs essentially depends on the MAPKAPs, MK2, and MK3 (MK2/3) downstream of MyD88. In contrast to this, the IL‐33‐induced and MyD88‐dependent IL‐2 production in mast cells contributes to the maintenance of Helios + T regs . Thereby, the IL‐33‐induced IL‐2 response and, thus, the maintenance of Helios + T regs are limited by an IL‐6‐mediated autocrine negative feedback stimulation acting on mast cells. Collectively, we present MK2/3 in IL‐33‐activated mast cells as a signaling node, which controls the dichotomy between RORγt + T reg and Helios + T reg in vitro. Abstract : IL‐33 induces the MK2/3‐Erk1/2‐STAT3 signalling module which results in IL‐6 and IL‐2 production by mast cells. In presence of TCR activation, this IL‐6 induces the formation of RORγt + Tregs and simultaneously balances the IL‐2‐dependent maintenance of Helios + Tregs by inducing an autocrine negative feedback loop on mast cells.