TRAF3 is critical for initial T follicular helper cell specification via coordination of the IL-6R/IL-2R-BCL6 signaling nexus.

ABSTRACT: CD4⁺ T follicular helper (T_FH) cells are essential for orchestrating robust humoral immunity, yet the signals that initiate T_FH cell differentiation are not fully understood. We identified that the adapter protein TRAF3 was required for T_FH cell differentiation and function during systemic inflammatory infections. Loss of CD4⁺ T cell-intrinsic TRAF3 impaired chromatin remodeling and transcriptional programming essential for T_FH cell initiation and instead augmented T_H1 development and function. TRAF3-deficient CD4⁺ T cells exhibited altered interleukin-6 (IL-6) and IL-2 responsiveness, which were coupled to failures in BCL6 expression. Enforced expression of either IL-6 receptor or BCL6 or blockade of I

SUBMITTER: Shao P 

PROVIDER: S-EPMC12315785 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature