PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation.

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-beta. In the absence of Runx3, DC become insensitive to TGF-beta-induced maturation inhibition, and TGF-beta-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 beta2-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.
PMID
Related Publications

Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent transcriptional regulation by Runx3.

Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage.

Runx3 regulates dendritic epidermal T cell development.

Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis.

Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4-/CD8+ T cells.

Authors

Mayor MeshTerms
Keywords
Journal Title the embo journal
Publication Year Start




PMID- 14765120
OWN - NLM
STAT- MEDLINE
DA  - 20040226
DCOM- 20050719
LR  - 20140610
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 23
IP  - 4
DP  - 2004 Feb 25
TI  - Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence
      results in airway inflammation.
PG  - 969-79
AB  - 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-beta. In the absence of Runx3, DC become
      insensitive to TGF-beta-induced maturation inhibition, and TGF-beta-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 beta2-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.
FAU - Fainaru, Ofer
AU  - Fainaru O
AD  - Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot,
      Israel.
FAU - Woolf, Eilon
AU  - Woolf E
FAU - Lotem, Joseph
AU  - Lotem J
FAU - Yarmus, Merav
AU  - Yarmus M
FAU - Brenner, Ori
AU  - Brenner O
FAU - Goldenberg, Dalia
AU  - Goldenberg D
FAU - Negreanu, Varda
AU  - Negreanu V
FAU - Bernstein, Yael
AU  - Bernstein Y
FAU - Levanon, Ditsa
AU  - Levanon D
FAU - Jung, Steffen
AU  - Jung S
FAU - Groner, Yoram
AU  - Groner Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040205
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Antigens, CD18)
RN  - 0 (Core Binding Factor Alpha 3 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Runx3 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Antigens, CD18/biosynthesis
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Cells, Cultured
MH  - Core Binding Factor Alpha 3 Subunit
MH  - DNA-Binding Proteins/biosynthesis/genetics/*physiology
MH  - Dendritic Cells/*metabolism/pathology
MH  - Eosinophils/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mucus/secretion
MH  - Pneumonia/*immunology/pathology
MH  - Pulmonary Alveoli/pathology
MH  - Signal Transduction
MH  - T-Lymphocytes/metabolism/pathology
MH  - Transcription Factors/biosynthesis/genetics/*physiology
MH  - Transforming Growth Factor beta/*physiology
PMC - PMC380997
OID - NLM: PMC380997
EDAT- 2004/02/07 05:00
MHDA- 2005/07/20 09:00
CRDT- 2004/02/07 05:00
PHST- 2003/10/15 [received]
PHST- 2003/12/18 [accepted]
AID - 10.1038/sj.emboj.7600085 [doi]
AID - 7600085 [pii]
PST - ppublish
SO  - EMBO J. 2004 Feb 25;23(4):969-79. Epub 2004 Feb 5.