Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammation

Yingyu Ma, Hongtao Liu, Hoang Tu-Rapp, Hans Juergen Thiesen, Saleh M. Ibrahim, Shawn M. Cole, Richard M Pope*

*Corresponding author for this work

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

The nonapoptotic functions of Fas ligation are incompletely characterized. In contrast to expectations, we show here that Fas-deficient mice developed less-severe collagen-induced arthritis than did control mice. Despite having milder arthritis, Fas-deficient mice had more of the critical pro-inflammatory mediator interleukin-1β (IL-1β) in their joints, suggesting inefficient activation through IL-1 receptor 1 (IL-1R1) when Fas signaling is deficient. In primary human macrophages and macrophages from Fas- or Fas ligand (FasL -deficient mice, interruption of Fas-FasL signaling suppressed nuclear factor-κB activation and cytokine expression induced by IL-1β and lipopolysaccharide. This cross-talk was mediated by the Fas-associated death domain through interaction with myeloid differentiation factor 88. These observations document a unique mechanism whereby Fas-FasL interactions enhance activation through the IL-1R1 or Toll-like receptor 4 pathway, which may contribute to the pathogenesis of chronic arthritis.

Original languageEnglish (US)
Pages (from-to)380-387
Number of pages8
JournalNature Immunology
Volume5
Issue number4
DOIs
StatePublished - Apr 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammation'. Together they form a unique fingerprint.

  • Cite this