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Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.

Publication ,  Journal Article
Hammer, GE; Turer, EE; Taylor, KE; Fang, CJ; Advincula, R; Oshima, S; Barrera, J; Huang, EJ; Hou, B; Malynn, BA; Reizis, B; DeFranco, A ...
Published in: Nat Immunol
October 23, 2011

Dendritic cells (DCs), which are known to support immune activation during infection, may also regulate immune homeostasis in resting animals. Here we show that mice lacking the ubiquitin-editing molecule A20 specifically in DCs spontaneously showed DC activation and population expansion of activated T cells. Analysis of DC-specific epistasis in compound mice lacking both A20 and the signaling adaptor MyD88 specifically in DCs showed that A20 restricted both MyD88-independent signals, which drive activation of DCs and T cells, and MyD88-dependent signals, which drive population expansion of T cells. In addition, mice lacking A20 specifically in DCs spontaneously developed lymphocyte-dependent colitis, seronegative ankylosing arthritis and enthesitis, conditions stereotypical of human inflammatory bowel disease (IBD). Our findings indicate that DCs need A20 to preserve immune quiescence and suggest that A20-dependent DC functions may underlie IBD and IBD-associated arthritides.

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Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

October 23, 2011

Volume

12

Issue

12

Start / End Page

1184 / 1193

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • T-Lymphocytes
  • Spondylitis, Ankylosing
  • Splenomegaly
  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Nuclear Proteins
  • Myeloid Differentiation Factor 88
  • Mice, Transgenic
 

Citation

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Hammer, G. E., Turer, E. E., Taylor, K. E., Fang, C. J., Advincula, R., Oshima, S., … Ma, A. (2011). Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol, 12(12), 1184–1193. https://doi.org/10.1038/ni.2135
Hammer, Gianna Elena, Emre E. Turer, Kimberly E. Taylor, Celia J. Fang, Rommel Advincula, Shigeru Oshima, Julio Barrera, et al. “Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.Nat Immunol 12, no. 12 (October 23, 2011): 1184–93. https://doi.org/10.1038/ni.2135.
Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, et al. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011 Oct 23;12(12):1184–93.
Hammer, Gianna Elena, et al. “Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.Nat Immunol, vol. 12, no. 12, Oct. 2011, pp. 1184–93. Pubmed, doi:10.1038/ni.2135.
Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011 Oct 23;12(12):1184–1193.

Published In

Nat Immunol

DOI

EISSN

1529-2916

Publication Date

October 23, 2011

Volume

12

Issue

12

Start / End Page

1184 / 1193

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • T-Lymphocytes
  • Spondylitis, Ankylosing
  • Splenomegaly
  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Nuclear Proteins
  • Myeloid Differentiation Factor 88
  • Mice, Transgenic