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Runx3 regulates mouse TGF‐β‐mediated dendritic cell function and its absence results in airway inflammation
Author(s) -
Fainaru Ofer,
Woolf Eilon,
Lotem Joseph,
Yarmus Merav,
Brenner Ori,
Goldenberg Dalia,
Negreanu Varda,
Bernstein Yael,
Leva Ditsa,
Jung Steffen,
Groner Yoram
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600085
Subject(s) - biology , inflammation , microbiology and biotechnology , dendritic cell , function (biology) , transforming growth factor , immunology , immune system
Runx3 transcription factor regulates cell lineage decisions in thymopoiesis and neurogenesis. Here we report that Runx3 knockout (KO) mice develop spontaneous eosinophilic lung inflammation associated with airway remodeling and mucus hypersecretion. Runx3 is specifically expressed in mature dendritic cells (DC) and mediates their response to TGF‐β. In the absence of Runx3, DC become insensitive to TGF‐β‐induced maturation inhibition, and TGF‐β‐dependent Langerhans cell development is impaired. Maturation of Runx3 KO DC is accelerated and accompanied by increased efficacy to stimulate T cells and aberrant expression of β2‐integrins. Lung alveoli of Runx3 KO mice accumulate DC characteristic of allergic airway inflammation. Taken together, abnormalities in DC function and subset distribution may constitute the primary immune system defect, which leads to the eosinophilic lung inflammation in Runx3 KO mice. These data may help elucidate the molecular mechanisms underlying the pathogenesis of allergic airway inflammation in humans.