KAP1 Regulates Regulatory T Cell Function and Proliferation in Both Foxp3-Dependent and -Independent Manners

Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease. KAP1-deficient Tregs failed to induce Foxp3-regulated Treg signature genes. In addition, KAP1-deficient Tregs were less proliferative due to the decreased expression of Slc1a5, whose expression was KAP1 dependent but Foxp3 independent. This reduced expression of Slc1a5 resulted in reduced mTORC1 activation. Thus, our data suggest that KAP1 regulates Treg function in a Foxp3-dependent manner and also controls Treg proliferation in a Foxp3-independent manner.