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

doi:10.1038/ni1054

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

Clinic of Dermatology, Allergology and Venerology

129 Citations (Scopus)

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 language	English
Journal	Nature Immunology
Volume	5
Issue number	4
Pages (from-to)	380-387
Number of pages	8
ISSN	1529-2908
DOIs	https://doi.org/10.1038/ni1054
Publication status	Published - 04.2004

Funding

also thank H. Perlman, P.H. Stern, N.A. Clipstone and A. Lin for critical review of the manuscript; M.E. Peter for advice on the immunoprecipitation experiments; C.J. Zander for technical assistance; and H.-J. Kreutzer for help evaluating joint histopathology. Supported by the National Institutes of Health (R01-AR049217) and The Veterans Administration Research Service (Merit Review), the National and Greater Chicagoland Chapters of the Arthritis Foundation and Deutsche Forschungsgemeinschaft (IB 24/3-1 to S.M.I.).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Access to Document

10.1038/ni1054

Cite this

@article{414b39335e28425293ec8ed1563588d4,

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

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.",

author = "Yingyu Ma and Hongtao Liu and Hoang Tu-Rapp and Thiesen, \{Hans Juergen\} and Ibrahim, \{Saleh M.\} and Cole, \{Shawn M.\} and Pope, \{Richard M.\}",

note = "Funding Information: also thank H. Perlman, P.H. Stern, N.A. Clipstone and A. Lin for critical review of the manuscript; M.E. Peter for advice on the immunoprecipitation experiments; C.J. Zander for technical assistance; and H.-J. Kreutzer for help evaluating joint histopathology. Supported by the National Institutes of Health (R01-AR049217) and The Veterans Administration Research Service (Merit Review), the National and Greater Chicagoland Chapters of the Arthritis Foundation and Deutsche Forschungsgemeinschaft (IB 24/3-1 to S.M.I.).",

year = "2004",

month = apr,

doi = "10.1038/ni1054",

language = "English",

volume = "5",

pages = "380--387",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Research",

number = "4",

}

TY - JOUR

T1 - Fas ligation on macrophages enhances IL-1R1-Toll-like receptor 4 signaling and promotes chronic inflammation

AU - Ma, Yingyu

AU - Liu, Hongtao

AU - Tu-Rapp, Hoang

AU - Thiesen, Hans Juergen

AU - Ibrahim, Saleh M.

AU - Cole, Shawn M.

AU - Pope, Richard M.

N1 - Funding Information: also thank H. Perlman, P.H. Stern, N.A. Clipstone and A. Lin for critical review of the manuscript; M.E. Peter for advice on the immunoprecipitation experiments; C.J. Zander for technical assistance; and H.-J. Kreutzer for help evaluating joint histopathology. Supported by the National Institutes of Health (R01-AR049217) and The Veterans Administration Research Service (Merit Review), the National and Greater Chicagoland Chapters of the Arthritis Foundation and Deutsche Forschungsgemeinschaft (IB 24/3-1 to S.M.I.).

PY - 2004/4

Y1 - 2004/4

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/5044228305

U2 - 10.1038/ni1054

DO - 10.1038/ni1054

M3 - Journal articles

C2 - 15004557

AN - SCOPUS:5044228305

SN - 1529-2908

VL - 5

SP - 380

EP - 387

JO - Nature Immunology

JF - Nature Immunology

IS - 4

ER -

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

Abstract

Funding

UN SDGs

Research Areas and Centers

Access to Document

Other files and links

Fingerprint

Cite this