T helper (Th) cells are critical for defenses against infection and recognize peptides bound to class II major histocompatibility complex (MHC II) molecules. Although transcription factors have been identified that direct Th cells into specific effector fates, whether a " master" regulator controls the developmental program common to all Th cells remains unclear. Here, we showed that the two transcription factors Thpok and LRF share this function. Although disruption of both factors did not prevent the generation of MHC II-specific T cells, these cells failed to express Th cell genes or undergo Th cell differentiation in vivo. In contrast, T cells lacking Thpok, which only displayed LRF-dependent functions, contributed to multiple effector responses, both in vitro and in vivo, with the notable exception of Th2 cell responses that control extracellular parasites. These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function.
Bibliographical noteFunding Information:
We thank P.P. Pandolfi for Zbtb7a mutant mice, N. Bouladoux for assistance with L. major experiments, B. Taylor and S. Banerjee for cell sorting, L. Williams and Q. Xiao for help with experiments, K. Beacht, E. Castro, and L. Stepanian for expert mouse technical support, M. Mehaffey, B. Tran, and Y. Zhao for assistance with Chipseq analyses, and J. Ashwell, A. Gégonne, J. Konkel, P. Schwartzberg, and M. Vacchio for reading the manuscript. This work benefitted from data assembled by the ImmGen consortium. This work was supported by the Intramural Research Programs of the National Cancer Institute, Center for Cancer Research, of the National Institute of Allergy and Infectious Diseases, and of the National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health.