1. MALT1 protease function in regulatory T cells induces MYC activity to promote mitochondrial function and cellular expansion
- Author
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Jürgen Ruland, Ritu Mishra, Theresa Mitterer, Christin Weiß, Theresa Schnalzger, Marc Rosenbaum, Roland Rad, Cora Mibus, and Thomas Engleitner
- Subjects
Effector ,Immunology ,T-cell receptor ,Mice, Transgenic ,hemic and immune systems ,chemical and pharmacologic phenomena ,Paracaspase ,Biology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,ddc ,Mitochondria ,Cell biology ,Proto-Oncogene Proteins c-myc ,Mice ,MALT1 ,Downregulation and upregulation ,Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ,Animals ,Immunology and Allergy ,Signal transduction ,Transcription factor ,Tissue homeostasis ,Cell Proliferation - Abstract
Regulatory T cells (Tregs) are essential for the inhibition of immunity and the maintenance of tissue homeostasis. Signals from the T-cell antigen receptor (TCR) are critical for early Treg development, their expansion, and inhibitory activity. Although TCR-engaged activation of the paracaspase MALT1 is important for these Treg activities, the MALT1 effector pathways in Tregs remain ill-defined. Here, we demonstrate that MALT1 protease activity controls the TCR-induced upregulation of the transcription factor MYC and the subsequent expression of MYC target genes in Tregs. These mechanisms are important for Treg-intrinsic mitochondrial function, optimal respiratory capacity, and homeostatic Treg proliferation. Consistently, conditional deletion of Myc in Tregs results similar to MALT1 inactivation in a lethal autoimmune inflammatory syndrome. Together, these results identify a MALT1 protease-mediated link between TCR signaling in Tregs and MYC control that coordinates metabolism and Treg expansion for the maintenance of immune homeostasis.
- Published
- 2021
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