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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • October 23, 2011

Published In

Volume / Issue

  • 12 / 12

Start / End Page

  • 1184 - 1193

PubMed ID

  • 22019834

Pubmed Central ID

  • 22019834

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

Digital Object Identifier (DOI)

  • 10.1038/ni.2135

Language

  • eng

Conference Location

  • United States