Figure 7. Proposed mechanism of TLR4-dependent regulation of TCR activation (conditional activation).
TLR4 triggering of CD4+ T cells activates NF-κB and MAPK pathways. However, the induction of MKP1 and MKP3 occurs mainly via the TRIF pathway. The high levels of MKP-1 and MKP-3 restrain a subsequent TCR-dependent activation of p38 and ERK, respectively. This activation of phosphatases in CD4+ T cells by TLR4 restrains subsequent TCR-induced phosphorylation events and, hence, modulates CD4+ T cell responses and their inflammatory phenotypes. AP-1, activator protein 1; MKK, MAPK kinase.