First Author | Heger K | Year | 2014 |
Journal | PLoS Biol | Volume | 12 |
Issue | 1 | Pages | e1001762 |
PubMed ID | 24453940 | Mgi Jnum | J:208446 |
Mgi Id | MGI:5563307 | Doi | 10.1371/journal.pbio.1001762 |
Citation | Heger K, et al. (2014) A20-deficient mast cells exacerbate inflammatory responses in vivo. PLoS Biol 12(1):e1001762 |
abstractText | Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-kappaB negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/FcepsilonRI, TLRs, IL-1R, and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation, late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated, in contrast to experimental autoimmune encephalomyelitis and immediate anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can exacerbate inflammatory disorders and define diseases that might benefit from therapeutic intervention with mast cell function. |