| First Author | Merkley SD | Year | 2022 |
| Journal | J Crohns Colitis | Volume | 16 |
| Issue | 2 | Pages | 259-274 |
| PubMed ID | 34374750 | Mgi Jnum | J:329183 |
| Mgi Id | MGI:7341921 | Doi | 10.1093/ecco-jcc/jjab144 |
| Citation | Merkley SD, et al. (2022) Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12 Prevents Gut Dysbiosis and Inflammation. J Crohns Colitis 16(2):259-274 |
| abstractText | Intestinal myeloid cells play a critical role in balancing intestinal homeostasis and inflammation. Here, we report that expression of the autophagy-related 5 [Atg5] protein in myeloid cells prevents dysbiosis and excessive intestinal inflammation by limiting IL-12 production. Mice with a selective genetic deletion of Atg5 in myeloid cells [Atg5DeltaMye] showed signs of dysbiosis preceding colitis, and exhibited severe intestinal inflammation upon colitis induction that was characterised by increased IFNgamma production. The exacerbated colitis was linked to excess IL-12 secretion from Atg5-deficient myeloid cells and gut dysbiosis. Restoration of the intestinal microbiota or genetic deletion of IL-12 in Atg5DeltaMye mice attenuated the intestinal inflammation in Atg5DeltaMye mice. Additionally, Atg5 functions to limit IL-12 secretion through modulation of late endosome [LE] acidity. Last, the autophagy cargo receptor NBR1, which accumulates in Atg5-deficient cells, played a role by delivering IL-12 to LE. In summary, Atg5 expression in intestinal myeloid cells acts as an anti-inflammatory brake to regulate IL-12, thus preventing dysbiosis and uncontrolled IFNgamma-driven intestinal inflammation. |
