DUSP6 mediates T cell receptor-engaged glycolysis and restrains T_FH cell differentiation.

ABSTRACT: Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6^-/-), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (T_FH) cell differentiation and T cell metabolism. In vitro, DUSP6^-/- CD4⁺ T_FH cells produced elevated IL-21. In vivo, T_FH cells were increased in DUSP6^-/- mice and in transgenic OTII-DUSP6^-/- mice at steady state. After immunization, DUSP6^-/- and OTII-DUSP6^-/- mice generated more T_FH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6^-/- T cells showed enhanced JNK and p38

SUBMITTER: Hsu WC 

PROVIDER: S-EPMC6112722 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature