Regulation of Egr2 expression in T cells and Egr2/3 function in tumour infiltrating T cells

Abstract

The immune system is an organism’s defence to protect the body against invading pathogens. T cells are one of the major components and essential for immune responses. The early growth response gene (Egr2) in T cells is important for maintaining immune functions of T cells by promoting adaptive immune responses, while controlling inflammation and preventing the development of autoimmune diseases. A recent study by our group demonstrated the function of Egr2 as a checkpoint regulator controlling the proliferation and differentiation of the T cells. In association, Egr2 and 3 play an indispensable role in the T cell immune response, but its function in tumour regression is less well known. Also, the mechanism regulating Egr2 expression in T cells is still unclear. In this study, Egr2 was found to be significantly induced in tumour infiltrating lymphocytes (TILs) in a mouse melanoma tumour model. Deficiency of Egr2 and 3 resulted in rapid growth of tumour with impaired TIL expansion. The reduced expansion of TILs in Egr2/3 deficient mice were impaired in IL-2 production and expressed low levels of proliferation marker Ki-67, suggesting the positive role of Egr2 in CD8+ TIL expansion and tumour regression. Furthermore, Egr2 expression was regulated by antigens and cytokines including, IL-2, IL-4 and IFNγ, IL-6. The latter regulatory function was mediated by IFNγ/STAT1 and IL-6/STAT3 signalling pathways.