Interleukin 1 Receptor Associated Kinase 3 (IRAK3)

IRAKM prevented dissociation of IRAK and IRAK4 from MYD88 and formation of IRAK-TRAF6 complexes. IRAKM cells exhibited increased cytokine production upon TLR/IL1 stimulation and bacterial challenge, and Irakm mice showed increased inflammatory responses to bacterial infection. Endotoxin tolerance, a protection mechanism against endotoxin shock, was significantly reduced in IRAKM -/- cells. Thus, the authors concluded that IRAKM regulates TLR signaling and innate immune homeostasis. Blood monocytes from leukemia patients and patients with metastatic disease also overexpressed IRAKM. Induction of IRAKM by hyaluronan could be blocked by anti-CD44 or anti-TLR4. TNF mRNA and protein expression by monocytes was upregulated by treatment with small interfering RNA to IRAKM.