Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity.
Atretkhany KN, Mufazalov IA, Dunst J, Kuchmiy A, Gogoleva VS, Andruszewski D, Drutskaya MS, Faustman DL, Schwabenland M, Prinz M, Kruglov AA, Waisman A, Nedospasov SA
Proc Natl Acad Sci U S A. online article
TNF is a multifunctional cytokine involved in autoimmune disease pathogenesis that exerts its effects through two distinct TNF receptors, TNFR1 and TNFR2. While TNF- and TNFR1-deficient (but not TNFR2-deficient) mice show very similar phenotypes, the significance of TNFR2 signaling in health and disease remains incompletely understood. Recent studies implicated the importance of the TNF/TNFR2 axis in T regulatory (Treg) cell functions. To definitively ascertain the significance of TNFR2 signaling, we generated and validated doubly humanized TNF/TNFR2 mice, with the option of conditional inactivation of TNFR2. Our findings expose the intrinsic and beneficial effects of TNFR2 signaling in Treg cells that could translate into protective functions in vivo, including treatment of autoimmunity.
