Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Jurkin, J; Krump, C; Köffel, R; Fieber, C; Schuster, C; Brunner, PM; Borek, I; Eisenwort, G; Lim, C; Mages, J; Lang, R; Bauer, W; Mechtcheriakova, D; Meshcheryakova, A; Elbe-Bürger, A; Stingl, G; Strobl, H.
Human skin dendritic cell fate is differentially regulated by the monocyte identity factor Kruppel-like factor 4 during steady state and inflammation.
J Allergy Clin Immunol. 2017; 139(6):1873-1884
Doi: 10.1016/j.jaci.2016.09.018
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- Führende Autor*innen der Med Uni Graz
- Krump Corinna
- Strobl Herbert
- Co-Autor*innen der Med Uni Graz
- Borek Izabela Malgorzata
- Köffel René
- Lim Clarice
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- Abstract:
- Langerhans cell (LC) networks play key roles in immunity and tolerance at body surfaces. LCs are established prenatally and can be replenished from blood monocytes. Unlike skin-resident dermal DCs (dDCs)/interstitial-type DCs and inflammatory dendritic epidermal cells appearing in dermatitis/eczema lesions, LCs lack key monocyte-affiliated markers. Inversely, LCs express various epithelial genes critical for their long-term peripheral tissue residency. Dendritic cells (DCs) are functionally involved in inflammatory diseases; however, the mechanisms remained poorly understood. In vitro differentiation models of human DCs, gene profiling, gene transduction, and immunohistology were used to identify molecules involved in DC subset specification. Here we identified the monocyte/macrophage lineage identity transcription factor Kruppel-like factor 4 (KLF4) to be inhibited during LC differentiation from human blood monocytes. Conversely, KLF4 is maintained or induced during dermal DC and monocyte-derived dendritic cell/inflammatory dendritic epidermal cell differentiation. We showed that in monocytic cells KLF4 has to be repressed to allow their differentiation into LCs. Moreover, respective KLF4 levels in DC subsets positively correlate with proinflammatory characteristics. We identified epithelial Notch signaling to repress KLF4 in monocytes undergoing LC commitment. Loss of KLF4 in monocytes transcriptionally derepresses Runt-related transcription factor 3 in response to TGF-β1, thereby allowing LC differentiation marked by a low cytokine expression profile. Monocyte differentiation into LCs depends on activation of Notch signaling and the concomitant loss of KLF4. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Cell Differentiation - physiology
- Cells, Cultured -
- Dendritic Cells - cytology
- Dendritic Cells - metabolism
- Embryo, Mammalian -
- Fetal Blood - cytology
- Humans -
- Inflammation - metabolism
- Kruppel-Like Transcription Factors - metabolism
- Monocytes - cytology
- Monocytes - metabolism
- Skin - cytology
- Transforming Growth Factor beta1 - pharmacology
- Find related publications in this database (Keywords)
- Kruppel-like factor 4
- Runt-related transcription factor 3
- TGF-beta 1 signaling
- Notch
- lineage decision
- monocyte differentiation