Article
- The EMBO Journal (2004) 23, 969 - 979
- doi:10.1038/sj.emboj.7600085
Published online: 5 February 2004
Subject Categories:
Runx3 regulates mouse TGF-
-mediated dendritic cell function and its absence results in airway inflammation
Ofer Fainaru1, Eilon Woolf1, Joseph Lotem1, Merav Yarmus1, Ori Brenner2, Dalia Goldenberg1, Varda Negreanu1, Yael Bernstein1, Ditsa Levanon1, Steffen Jung3 and Yoram Groner1
- Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
- Department of Veterinary Resources, The Weizmann Institute of Science, Rehovot, Israel
- Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel
Correspondence to:
Yoram Groner, Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. Tel.: +972 8 934 3972; Fax: +972 8 934 4108; E-mail: yoram.groner@weizmann.ac.il
Received 15 October 2003; Accepted 18 December 2003
Abstract
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-
. In the absence of Runx3, DC become insensitive to TGF--induced maturation inhibition, and TGF--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 2-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.
Keywords:
- airway inflammation,
- knockout mice,
- lung eosinophilia,
- Runx3 transcription factor,
- TGF- signaling
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