| First Author | Zhang M | Year | 2017 |
| Journal | Am J Respir Cell Mol Biol | Volume | 57 |
| Issue | 5 | Pages | 547-559 |
| PubMed ID | 28665693 | Mgi Jnum | J:266799 |
| Mgi Id | MGI:6220853 | Doi | 10.1165/rcmb.2016-0370OC |
| Citation | Zhang M, et al. (2017) Critical Role of IRAK-M in Regulating Antigen-Induced Airway Inflammation. Am J Respir Cell Mol Biol 57(5):547-559 |
| abstractText | Asthma is an airway epithelium disorder involving allergic lung inflammation. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of Toll-like receptor (TLR) signaling on airway epithelial cells and macrophages, and it is known to limit the overproduction of cytokines during the inflammatory process. However, the direct role of IRAK-M in asthma pathogenesis is unclear. In the present study, we found a significant elevation of IRAK-M expression in mouse lungs after ovalbumin (OVA) exposure. Compared with wild-type mice, IRAK-M knockout (KO) mice responded to OVA challenge with significantly worse infiltration of airway inflammatory cells, greater airway responsiveness, higher proinflammatory cytokine levels in lung homogenates, and more prominent T-helper cell type 2 (Th2) and Th17 deviation. OVA exposure also induced higher activities of dendritic cells (DCs) and macrophages from IRAK-M KO mouse lungs. Furthermore, adoptive transfer of either IRAK-M KO bone-marrow-derived DCs or macrophages into wild-type mice aggravated OVA-induced airway inflammation. In vitro experiments showed that IRAK-M KO naive CD4(+) T cells were more prone to differentiate into Th17 cells, but not regulatory T cells. Consistently, activation of IkappaBzeta was significantly increased in the absence of IRAK-M, facilitating Th17 polarization. These findings suggest that IRAK-M plays a crucial role in the regulation of allergic airway inflammation by modifying the function of airway epithelia, DCs, and macrophages, and the differentiation of naive CD4(+) T cells. Modulation of IRAK-M may provide a novel target for the control of asthma. |
