[The functions of CD4+CD25-LAG3+ regulatory T cells and Egr2 in the regulation of autoimmunity].
Regulatory T cells (Treg) are important mechanisms that regulate autoimmunity and CD4+CD25+Foxp3+ regulatory T cells (CD25+Treg) have been extensively investigated. Recently, we have identified CD4+CD25-LAG3+ regulatory T cells (LAG3+Treg) that express an anergy associated transcription factor Egr2. Egr2 regulates IL-10 production in response to IL-27, and Egr2-deficiency in T cells and B cells results in systemic autoimmunity with increased IL-17 production. Moreover, addition of Egr3 deficiency to Egr2-deficient mice significantly accelerates systemic autoimmunity without functional impairment of CD25+Treg, indicating cooperative autoimmune-regulation by Egr2 and Egr3. The linkage between Egr2 and systemic autoimmunity is also suggested by the fact that stimulation with Ly108, a candidate lupus susceptibility gene in lupus-prone NZM2410 mice, induces Egr2 expression in T cells. Collectively, LAG3+Treg and Egr2 are the unique regulators of autoimmunity and further examination may help to understand and control immune responses.
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.
Keishi
K
Fujio
Tomohisa
T
Okamura
Shuji
S
Sumitomo
Kazuhiko
K
Yamamoto
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D015551:Autoimmunity / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D051767:Early Growth Response Protein 2 / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D015704:CD4 Antigens; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse