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

Gianna Elena Hammer, Emre E. Turer, Kimberly E. Taylor, Celia J. Fang, Rommel Advincula, Shigeru Oshima, Julio Barrera, Eric J. Huang, Baidong Hou, Barbara A. Malynn, Boris Reizis, Anthony Defranco, Lindsey A. Criswell, Mary C. Nakamura, Averil Ma

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1184-1193
Number of pages10
JournalNature Immunology
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2011

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Colitis
Dendritic Cells
Homeostasis
Inflammatory Bowel Diseases
T-Lymphocytes
Arthritis
Ubiquitin
Population
Lymphocytes
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. / Hammer, Gianna Elena; Turer, Emre E.; Taylor, Kimberly E.; Fang, Celia J.; Advincula, Rommel; Oshima, Shigeru; Barrera, Julio; Huang, Eric J.; Hou, Baidong; Malynn, Barbara A.; Reizis, Boris; Defranco, Anthony; Criswell, Lindsey A.; Nakamura, Mary C.; Ma, Averil.

In: Nature Immunology, Vol. 12, No. 12, 01.12.2011, p. 1184-1193.

Research output: Contribution to journalArticle

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 2011, 'Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis', Nature Immunology, vol. 12, no. 12, pp. 1184-1193. https://doi.org/10.1038/ni.2135
Hammer, Gianna Elena ; Turer, Emre E. ; Taylor, Kimberly E. ; Fang, Celia J. ; Advincula, Rommel ; Oshima, Shigeru ; Barrera, Julio ; Huang, Eric J. ; Hou, Baidong ; Malynn, Barbara A. ; Reizis, Boris ; Defranco, Anthony ; Criswell, Lindsey A. ; Nakamura, Mary C. ; Ma, Averil. / Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. In: Nature Immunology. 2011 ; Vol. 12, No. 12. pp. 1184-1193.
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