Signaling through the Adaptor Molecule MyD88 in CD4+ T Cells Is Required to Overcome Suppression by Regulatory T Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 40; no. 1; pp. 78 - 90
• Main Authors: Schenten, Dominik, Nish, Simone A., Yu, Shuang, Yan, Xiting, Lee, Heung Kyu, Brodsky, Igor, Pasman, Lesley, Yordy, Brian, Wunderlich, F. Thomas, Brüning, Jens C., Zhao, Hongyu, Medzhitov, Ruslan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.01.2014; Elsevier Limited
• Subjects: Adaptive Immunity; Animals; Bone marrow; Cells, Cultured; Cloning; Experiments; Flow cytometry; Immune system; Immunity, Innate; Immunologic Memory; Immunosuppression; Interleukin-1 - metabolism; Interleukin-18 - metabolism; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Organ Specificity; Receptors, Interleukin-1 - metabolism; Signal Transduction - genetics; Signal Transduction - immunology; Software; Studies; T cell receptors; T-Lymphocytes, Regulatory - immunology; Th1 Cells - immunology; Th17 Cells - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.10.023

Innate immune recognition controls adaptive immune responses through multiple mechanisms. The MyD88 signaling adaptor operates in many cell types downstream of Toll-like receptors (TLRs) and interleukin-1 (IL-1) receptor family members. Cell-type-specific functions of MyD88 signaling remain poorly characterized. Here, we have shown that the T cell-specific ablation of MyD88 in mice impairs not only T helper 17 (Th17) cell responses, but also Th1 cell responses. MyD88 relayed signals of TLR-induced IL-1, which became dispensable for Th1 cell responses in the absence of T regulatory (Treg) cells. Treg cell-specific ablation of MyD88 had no effect, suggesting that IL-1 acts on naive CD4+ T cells instead of Treg cells themselves. Together, these findings demonstrate that IL-1 renders naive CD4+ T cells refractory to Treg cell-mediated suppression in order to allow their differentiation into Th1 cells. In addition, IL-1 was also important for the generation of functional CD4+ memory T cells. •Ablation of MyD88 in T cells impairs both Th1 and Th17 cell responses•Defect is due to abrogated IL-1 signaling•Th1 cell response is recovered in the absence of Treg cells•IL-1 acts on naive or effector CD4+ T cells and not on Treg cells