| First Author | Kobayashi K | Year | 2002 |
| Journal | Cell | Volume | 110 |
| Issue | 2 | Pages | 191-202 |
| PubMed ID | 12150927 | Mgi Jnum | J:78189 |
| Mgi Id | MGI:2183694 | Doi | 10.1016/s0092-8674(02)00827-9 |
| Citation | Kobayashi K, et al. (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110(2):191-202 |
| abstractText | Toll-like receptors (TLRs) detect microorganisms and protect multicellular organisms from infection. TLRs transduce their signals through MyD88 and the serine/threonine kinase IRAK. The IRAK family consists of two active kinases, IRAK and IRAK-4, and two inactive kinases, IRAK-2 and IRAK-M. IRAK-M expression is restricted to monocytes/macrophages, whereas other IRAKs are ubiquitous. We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. IRAK-M(-/-) cells exhibited increased cytokine production upon TLR/IL-1 stimulation and bacterial challenge, and IRAK-M(-/-) mice showed increased inflammatory responses to bacterial infection. Endotoxin tolerance, a protection mechanism against endotoxin shock, was significantly reduced in IRAK-M(-/-) cells. Thus, IRAK-M regulates TLR signaling and innate immune homeostasis. |
