TRIF–GEFH1–RhoB pathway is involved in MHCII expression on dendritic cells that is critical for CD4 T-cell activation

Abstract

Dendritic cells (DC) play a central role in immune responses by presenting antigenic peptides to CD4+ T cells through MHCII molecules. Here, we demonstrate a TRIF–GEFH1–RhoB pathway is involved in MHCII surface expression on DC. We show the TRIF (TIR domain‐containing adapter inducing IFNβ)‐ but not the myeloid differentiation factor 88 (MyD88)‐dependent pathway of lipopolysaccharide (LPS)‐signaling in DC is crucial for the MHCII surface expression, followed by CD4+ T‐cell activation. LPS increased the activity of RhoB, but not of RhoA, Cdc42, or Rac1/2 in a manor dependent on LPS‐TRIF‐ but not LPS‐Myd88‐signaling. RhoB colocalized with MHCII+ lysosomes in DC. A dominant‐negative (DN) form of RhoB (DN‐RhoB) or RhoB's RNAi in DC inhibited the LPS‐induced MHCII surface expression. Moreover, we found GEFH1 associated with RhoB, and DN‐GEFH1 or GEFH1's RNAi suppressed the LPS‐mediated RhoB activation and MHCII surface expression. DN‐RhoB attenuated the DC's CD4+ T‐cell stimulatory activity. Thus, our results provide a molecular mechanism relating how the MHCII surface expression is regulated during the maturation stage of DC. The activation of GEFH1‐RhoB through the TRIF‐dependent pathway of LPS in DC might be a critical target for controlling the activation of CD4+ T cells.