Transcriptome of CD4+ T cells from mice conditionally lacking YAP1 versus WT in different synthetic micromechanical environments

Upon immunogenic challenge, lymph nodes become mechanically stiff as immune cells activate and proliferate within their encapsulated environments, and with resolution, they reestablish a soft, baseline state. Here we show that sensing these mechanical changes in the microenvironment require the mechanosensor YAP. YAP is induced upon activation and suppresses metabolic reprogramming of effector T cells. Unlike in other cell types where YAP promotes proliferation, YAP in T cells suppresses proliferation in a stiffness-dependent manner by directly restricting the translocation of NFAT1 into the nucleus. YAP slows T-cell responses in systemic viral infections and retards effector T cells in autoimmune diabetes. Our work reveals a paradigm whereby tissue mechanics fine-tune adaptive immune responses in health and disease. Overall design: T-cell mRNA profiles of adult YAP fl/fl CD4-Cre-negative (WT) and YAP1 fl/fl CD4-Cre-positive (YAPcKO) mice