A role for the kinase activity of RIPK1 in survival of T lymphocytes during clonal expansion

Published: 11 April 2023| Version 1 | DOI: 10.17632/yw3chtjyc6.1


Receptor interacting protein kinase 1 (RIPK1) is a key molecule that regulates cell survival and cell death. Human inborn mutations that abrogate RIPK1 protein expression causes immunodeficiency marked by loss of effector/memory lymphocytes and very early onset inflammatory bowel disease. It is unclear how the loss of RIPK1 can lead to these disparate clinical phenotypes. To investigate the mechanism by which RIPK1 regulates effector T cell survival, we found that the acute loss of RIPK1 compromised activated T cell survival. Using mice that express a kinase inactive RIPK1, we showed that RIPK1 facilitates activated T cell survival during clonal expansion through its scaffold function as well as its kinase activity. Interestingly, loss of RIPK1 kinase activity impaired CD25 expression of activated T cells. Supplementation with recombinant IL-2 restored normal CD25 expression and survival of activated T cells. Our results show that RIPK1 regulates lymphocyte survival and homeostasis of T cells at different developmental stages through distinct mechanisms.



Zhejiang University


Life Sciences