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. 2012 Oct 29;3:322. doi: 10.3389/fimmu.2012.00322

Figure 2.

Figure 2

Regulatory function of TIR8/SIGIRR in signaling. TIR8/SIGIRR is a receptor composed by a single extracellular Ig domain (amino acids 17–112), a transmembrane domain (amino acids 117–139); an intracellular conserved TIR domain (amino acids 166–305), and a 95 amino acid-long intracellular tail. Two conserved amino acid (Ser, Tyr in TIR domain) necessary for IL-1R-signaling are replaced in TIR8/SIGIRR (Cys 222, Leu 305) potentially leading to a non-conventional activation. TIR8/SIGIRR is an orphan receptor, but IL-36Ra has been proposed as a TIR8/SIGIRR ligand in glial cells. TIR8/SIGIRR inhibits ILR (IL-1RI, IL-18R, T1/ST2) and TLR (TLR2, TLR3, TLR4, TLR5, TLR7/8, TLR9, and possibly others) signaling and NF-κB activation. In T cells and epithelial cells, TIR8/SIGIRR inhibits IL-1-dependent activation of the Akt-mTOR pathway and of JNK.