A20-deficient mast cells exacerbate inflammatory responses in vivo.

Abstract:

: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-κB negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/FcεRI, 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.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Heger K,Fierens K,Vahl JC,Aszodi A,Peschke K,Schenten D,Hammad H,Beyaert R,Saur D,van Loo G,Roers A,Lambrecht BN,Kool M,Schmidt-Supprian M

doi

10.1371/journal.pbio.1001762

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

e1001762

issue

1

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-13-02581

journal_volume

12

pub_type

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