Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Heinz, LX; Platzer, B; Reisner, PM; Jörgl, A; Taschner, S; Göbel, F; Strobl, H.
Differential involvement of PU.1 and Id2 downstream of TGF-beta1 during Langerhans-cell commitment.
Blood. 2006; 107(4):1445-1453
Doi: 10.1182/blood-2005-04-1721
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- Führende Autor*innen der Med Uni Graz
- Strobl Herbert
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- Abstract:
- Langerhans cells (LCs) are highly abundant dendritic cells (DCs) in epidermal and mucosal tissues. The transcription factors PU.1 and Id2 have been implicated as positive regulators of LC development from hematopoietic progenitor cells. LC differentiation from progenitors is absolutely dependent on transforming growth factor beta 1 (TGF-beta1) in vitro as well as in vivo; however, downstream mechanisms are poorly defined. We found that both PU.1 and Id2 are induced by TGF-beta1 in human CD34+ monocyte/LC (M/LC) progenitor cells, and that neither ectopic PU.1 or Id2 alone, nor both together, could replace TGF-beta1 in its instructive function on LC commitment. However, both factors critically contributed to LC differentiation by acting at 2 distinct intersection points. Ectopic PU.1 strongly enhanced TGF-beta1-dependent LC development. Additionally, Notch-induced generation of interstitial-type DCs was associated with PU.1 up-regulation. Thus, PU.1 is generally increased during myeloid DC development. Ectopic Id2 inhibits the acquisition of early monocytic characteristics by cells generated in the absence of TGF-beta1 and also inhibits monocyte induction by alternative stimuli. Since TGF-beta1 represses a default monocyte pathway of common progenitor cells, PU.1 and Id2 seem to modulate lineage options of M/LC precursors, downstream of TGF-beta1.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, CD - immunology
- Antigens, CD34 - immunology
- Cell Culture Techniques -
- DNA Primers -
- Fetal Blood - physiology
- Flow Cytometry -
- Gene Expression Regulation - immunology
- Humans -
- Infant, Newborn -
- Inhibitor of Differentiation Protein 2 - physiology
- Langerhans Cells - immunology
- Polymerase Chain Reaction -
- Stem Cells - immunology Stem Cells - physiology
- Transforming Growth Factor beta - physiology
- Transforming Growth Factor beta1 -