| First Author | Sorbara MT | Year | 2013 |
| Journal | Immunity | Volume | 39 |
| Issue | 5 | Pages | 858-73 |
| PubMed ID | 24238340 | Mgi Jnum | J:208987 |
| Mgi Id | MGI:5565525 | Doi | 10.1016/j.immuni.2013.10.013 |
| Citation | Sorbara MT, et al. (2013) The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner. Immunity 39(5):858-73 |
| abstractText | The peptidoglycan sensor Nod2 and the autophagy protein ATG16L1 have been linked to Crohn's disease (CD). Although Nod2 and the related sensor, Nod1, direct ATG16L1 to initiate anti-bacterial autophagy, whether ATG16L1 affects Nod-driven inflammation has not been examined. Here, we uncover an unanticipated autophagy-independent role for ATG16L1 in negatively regulating Nod-driven inflammatory responses. Knockdown of ATG16L1 expression, but not that of ATG5 or ATG9a, specifically enhanced Nod-driven cytokine production. In addition, autophagy-incompetent truncated forms of ATG16L1 regulated Nod-driven cytokine responses. Mechanistically, we demonstrated that ATG16L1 interfered with poly-ubiquitination of the Rip2 adaptor and recruitment of Rip2 into large signaling complexes. The CD-associated allele of ATG16L1 was impaired in its ability to regulate Nod-driven inflammatory responses. Overall, these results suggest that ATG16L1 is critical for Nod-dependent regulation of cytokine responses and that disruption of this Nod1- or Nod2-ATG16L1 signaling axis could contribute to the chronic inflammation associated with CD. |
