Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis
| Autor: | Eric J. Huang, Lindsey A. Criswell, Boris Reizis, Gianna E. Hammer, Barbara A. Malynn, Averil Ma, Mary C. Nakamura, Shigeru Oshima, Emre E. Turer, Celia J. Fang, Julio Barrera, Rommel Advincula, Kimberly E. Taylor, Baidong Hou, Anthony L. DeFranco |
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| Rok vydání: | 2011 |
| Předmět: |
Immunology
Population Arthritis chemical and pharmacologic phenomena Biology Inflammatory bowel disease 03 medical and health sciences 0302 clinical medicine Immune system immune system diseases hemic and lymphatic diseases medicine Immunology and Allergy Colitis education 030304 developmental biology 0303 health sciences education.field_of_study hemic and immune systems Tumor Necrosis Factor alpha-Induced Protein 3 medicine.disease 3. Good health Myeloid Differentiation Factor 88 Signal transduction 030215 immunology |
| Zdroj: | Nature Immunology. 12:1184-1193 |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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