Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion
Kim, Ji Hyung
MetadataShow full item record
CitationHu, Yu, Ji Hyung Kim, Kangmin He, Qi Wan, Jessica Kim, Melanie Flach, Tom Kirchhausen, Andrea Vortkamp, and Florian Winau. 2016. “Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion.” The Journal of Experimental Medicine 213 (12): 2759-2772. doi:10.1084/jem.20160612. http://dx.doi.org/10.1084/jem.20160612.
AbstractIn chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes. TMEM16F is located in late endosomes, where it facilitates the generation of multivesicular bodies for TCR degradation and signal termination. Consequently, TMEM16F deficiency results in sustained signaling and augmented T cell activation. Our results demonstrate that scramblase restricts TCR responses to avoid overactivation, ensuring a well-balanced immune response in chronic infectious disease.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:33029897
- HMS Scholarly Articles