TMEM126A, a CD137 ligand binding protein, couples with the TLR4 signal transduction pathway in macrophages

• The aim was to elucidate a role of TMEM126A in TLR4-mediated innate immune response.
• We have novel findings that TMEM126A is involved in late-phase TLR4 signals.
• These TLR4 signals engage in up-regulating gene expression for antigen presenting.
• This is the first study demonstrating a role of TMEM126A in TLR4 signaling.

We showed previously that a novel protein, transmembrane protein 126A (TMEM126A), binds to CD137 ligand (CD137L, 4-1BBL) and couples with its reverse signals in macrophages. Here, we present data showing that TMEM126A relays TLR4 signaling. Thus, up-regulation of CD54 (ICAM-1), MHC II, CD86 and CD40 expression in response to TLR4 activation was diminished in TMEM126A-deficient macrophages. Moreover in TMEM126A-deficient RAW264.7 cells, LPS/TLR4-induced late-phase JNK/SAPK and IRF-3 phosphorylation was abolished. These findings indicate that TMEM126A contributes to the TLR4 signal up-regulating the expression of genes whose products are involved in antigen presentation.