The Effects of TLR Activation on T-Cell Development and Differentiation

Figure 5

MyD88 signal pathway. MyD88 is the universal adaptor of all the identified TLRs except TLR3. In this figure, TLR1/TLR2 is used to illustrate the MyD88 signal pathway. TLR1/TLR2 uses triacryl lipopeptide as the ligand to recruit MyD88 via its cytoplasmic TIR domain. MyD88 interacts with DD to associate with IRAK4. IRAK4 then phosphorates IRAK1 and IRAK2 activates TRAF6. TRAF6 induces the synthesis of polyubiquitin chains that links TRAF6, NEMO, IRAK1 and TAB2, 3, 4. The ubiquitination of TAB2/3/4 in association with TAB1 activates TAK1. This induces phosphorylation of IKK complex resulting in the dissociation of IκB and NF-κB. NF-κB then translocates into nucleus to induce the gene transcription of proinflammatory cytokines. TAK1 also activates JNK and p38 which induce AP1 activation. MyD88 and TRAF6 both activate IRF5 and induce proinflammatory cytokines. This activation is inhibited by IRF4. TRAF6 also interacts with TRAF3 and then recruits TBK1 to activate IRF3 and IFN-β production. TRAF3 alternatively induces the anti-inflammatory cytokine IL-10.