IRGM restrains NLRP3 inflammasome activation by mediating its SQSTM1/p62-dependent selective autophagy

Subhash Mehto, Swati Chauhan, Kautilya Kumar Jena, Nishant Ranjan Chauhan, Parej Nath, Rinku Sahu, Kollori Dhar, Saroj Kumar Das, Santosh Chauhan

Research output: Contribution to journalComment/debatepeer-review

30 Scopus citations

Abstract

IRGM is an established genetic risk factor for Crohn disease (CD) and several other inflammatory disorders. However, the mechanisms employed by IRGM to restrain the inflammation are not known. In our recent study, we showed that IRGM negatively regulates NLRP3 inflammasome activation. IRGM employs 2 parallel approaches to constrain inflammasome activation. First, IRGM directly interacts with NLRP3 and PYCARD/ASC, and mediates their SQSTM1/p62-dependent macroautophagic/autophagic degradation. Second, IRGM impedes inflammasome assembly by blocking the polymerization of NLRP3 and PYCARD. We also found that IRGM suppresses NLRP3-mediated exacerbated outcomes of dextran sodium sulfate (DSS)-induced colitis in a mouse model. Taken together, this study presents evidence that IRGM can directly regulate inflammation and protect from inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)1645-1647
Number of pages3
JournalAutophagy
Volume15
Issue number9
DOIs
StatePublished - Sep 2 2019
Externally publishedYes

Keywords

  • Autophagy
  • Crohn disease
  • IRGM
  • IRGM1
  • NLRP3 inflammasome
  • inflammatory bowel disease

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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