title: The transcription factors Egr2 and Egr3 are essential for the control of inflammation and antigen-induced proliferation of B and T cells.
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.
authors.affiliation: Bioscience, Brunel University, UK.
authors.forename: Suling
authors.initials: S
authors.lastname: Li
authors.forename: Tizong
authors.initials: T
authors.lastname: Miao
authors.forename: Meera
authors.initials: M
authors.lastname: Sebastian
authors.forename: Punamdip
authors.initials: P
authors.lastname: Bhullar
authors.forename: Emma
authors.initials: E
authors.lastname: Ghaffari
authors.forename: Mengya
authors.initials: M
authors.lastname: Liu
authors.forename: Alistair L J
authors.initials: AL
authors.lastname: Symonds
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D051767:Early Growth Response Protein 2 / Q000172:deficiency / Q000276:immunology*; D051776:Early Growth Response Protein 3 / Q000172:deficiency / Q000276:immunology*; D006706:Homeostasis; D007249:Inflammation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018808:Transcription Factor AP-1 / Q000276:immunology
chemical_list: D000941:Antigens; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C497369:Egr3 protein, mouse; D018808:Transcription Factor AP-1; D051776:Early Growth Response Protein 3