CD40L modulates CD4⁺ T‐cell activation through receptor for activated C kinase 1

Abstract

Inhibition of the co‐stimulatory ligand CD40L has shown beneficial effects in many experimental models of auto‐immune disease and inflammation. Here, we show that CD40L deficiency in T‐cells in mice causes a reduction of CD4+ T cell activation and specifically a strong reduction in interferon‐ γ (IFN‐γ) producing T helper 1 (Th1) cells. In vitro, we could not reproduce this APC‐dependent effects, but found that T‐cell CD40L affects cell death and proliferation. We identified receptor of activated C kinase (RACK1), the canonical PKC binding partner and known to drive proliferation and apoptosis, as a mediator of CD40L reverse signaling. Furthermore, we found that CD40L clustering stabilizes IFN‐γ mediated Th1 polarization through STAT1, a known binding partner of RACK1. Together this highlights the importance of both CD40L forward and reverse signaling.This article is protected by copyright. All rights reserved

Exploring causal correlations between inflammatory cytokines and Ménière’s disease: a Mendelian randomization

“…DNER, a neuron-specific transmembrane protein with extracellular EGF-like repeats ( 44 ), has been demonstrated to facilitate prostate cancer advancement and enhance PC-3 cell proliferation by modulating the core genes associated with cancer stem cells ( 45 ). DNER was additionally discovered to be upregulated in gastric cancer, and its suppression led to inhibited growth and metastasis ( 46 ), also contributing to breast cancer progression by promoting stemness ( 47 ). STAM binding protein, or STAMBP, is a JAMM-family deubiquitinating enzyme with microtubule-interacting/transport and STAM-binding domains.…”