| First Author | Samie M | Year | 2018 |
| Journal | Nat Immunol | Volume | 19 |
| Issue | 3 | Pages | 246-254 |
| PubMed ID | 29358708 | Mgi Jnum | J:282423 |
| Mgi Id | MGI:6380874 | Doi | 10.1038/s41590-017-0042-6 |
| Citation | Samie M, et al. (2018) Selective autophagy of the adaptor TRIF regulates innate inflammatory signaling. Nat Immunol 19(3):246-254 |
| abstractText | Defective autophagy is linked to diseases such as rheumatoid arthritis, lupus and inflammatory bowel disease (IBD). However, the mechanisms by which autophagy limits inflammation remain poorly understood. Here we found that loss of the autophagy-related gene Atg16l1 promoted accumulation of the adaptor TRIF and downstream signaling in macrophages. Multiplex proteomic profiling identified SQSTM1 and Tax1BP1 as selective autophagy-related receptors that mediated the turnover of TRIF. Knockdown of Tax1bp1 increased production of the cytokines IFN-beta and IL-1beta. Mice lacking Atg16l1 in myeloid cells succumbed to lipopolysaccharide-mediated sepsis but enhanced their clearance of intestinal Salmonella typhimurium in an interferon receptor-dependent manner. Human macrophages with the Crohn's disease-associated Atg16l1 variant T300A exhibited more production of IFN-beta and IL-1beta. An elevated interferon-response gene signature was observed in patients with IBD who were resistant to treatment with an antibody to the cytokine TNF. These findings identify selective autophagy as a key regulator of signaling via the innate immune system. |
