1. The transcription factors Egr2 and Egr3 are essential for the control of inflammation and antigen-induced proliferation of B and T cells.
- Author
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Li S, Miao T, Sebastian M, Bhullar P, Ghaffari E, Liu M, Symonds AL, and Wang P
- Subjects
- Animals, Antigens immunology, Autoimmune Diseases immunology, Autoimmune Diseases pathology, B-Lymphocytes cytology, Early Growth Response Protein 2 deficiency, Early Growth Response Protein 3 deficiency, Homeostasis, Inflammation immunology, Mice, Mice, Knockout, Signal Transduction, T-Lymphocytes cytology, Transcription Factor AP-1 immunology, B-Lymphocytes immunology, Cell Proliferation, Early Growth Response Protein 2 immunology, Early Growth Response Protein 3 immunology, T-Lymphocytes immunology
- Abstract
Lymphocytes provide optimal responses against pathogens with minimal inflammatory pathology. However, the intrinsic mechanisms regulating these responses are unknown. Here, we report that deletion of both transcription factors Egr2 and Egr3 in lymphocytes resulted in a lethal autoimmune syndrome with excessive serum proinflammatory cytokines but also impaired antigen receptor-induced proliferation of B and T cells. Egr2- and Egr3-defective B and T cells had hyperactive signal transducer and activator of transcription-1 (STAT1) and STAT3 while antigen receptor-induced activation of transcription factor AP-1 was severely impaired. We discovered that Egr2 and/or Egr3 directly induced expression of suppressor of cytokine signaling-1 (SOCS1) and SOCS3, inhibitors of STAT1 and STAT3, and also blocked the function of Batf, an AP-1 inhibitor, in B and T cells. Thus, Egr2 and Egr3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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