Critical role for IL-18 in spontaneous lung inflammation caused by autophagy deficiency

Elmoataz Abdel Fattah, Abhisek Bhattacharya, Alan Herron, Zeenat Safdar, N. Tony Eissa

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Autophagy is an important component of the immune response. However, the functions of autophagy in human diseases are much less understood. We studied biological consequences of autophagy deficiency in mice lacking the essential autophagy gene Atg7 or Atg5 in myeloid cells. Surprisingly, these mice presented with spontaneous sterile lung inflammation, characterized by marked recruitment of inflammatory cells, submucosal thickening, goblet cell metaplasia, and increased collagen content. Lung inflammation was associated with increase in several proinflammatory cytokines in the bronchoalveolar lavage and in serum. This inflammation was largely driven by IL-18 as a result of constitutive inflammasome activation. Following i.p. LPS injection, autophagy-deficient mice had higher levels of proinflammatory cytokines in lungs and in serum, as well as increased mortality, than control mice. Intranasal bleomycin challenge exacerbated lung inflammation in autophagy-deficient mice and produced more severe fibrotic changes than in control mice. These results uncover a new and important role for autophagy as negative regulator of lung inflammation.

Original languageEnglish (US)
Pages (from-to)5407-5416
Number of pages10
JournalJournal of Immunology
Volume194
Issue number11
DOIs
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Critical role for IL-18 in spontaneous lung inflammation caused by autophagy deficiency'. Together they form a unique fingerprint.

Cite this