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

Mol Immunol. 2015 Apr;64(2):244-51. doi: 10.1016/j.molimm.2014.12.001. Epub 2014 Dec 27.

Abstract

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.

Keywords: Antigen presenting; CD137L; Innate immunity; TMEM126A; TRL4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • B7-2 Antigen / genetics
  • B7-2 Antigen / immunology
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology
  • Cell Line
  • Gene Expression Regulation
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / immunology
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / immunology
  • Macrophages, Peritoneal / cytology
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / immunology*
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Primary Cell Culture
  • Protein Binding
  • Signal Transduction / immunology*
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology

Substances

  • B7-2 Antigen
  • CD40 Antigens
  • Histocompatibility Antigens Class II
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Lipopolysaccharides
  • Membrane Proteins
  • TLR4 protein, human
  • TMEM126A protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Intercellular Adhesion Molecule-1
  • MAP Kinase Kinase 4