RT Journal Article SR Electronic T1 Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000766 DO 10.26508/lsa.202000766 VO 3 IS 9 A1 Symonds, Alistair LJ A1 Zheng, Wei A1 Miao, Tizong A1 Wang, Haiyu A1 Wang, TieShang A1 Kiome, Ruth A1 Hou, Xiujuan A1 Li, Suling A1 Wang, Ping YR 2020 UL http://www.life-science-alliance.org/content/3/9/e202000766.abstract AB The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2+ subset (PD-1high MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1high MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1high MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1high MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1high MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1high MP CD4 T cells and maintain their adaptive immune fitness.