Identification of Axl as a downstream effector of TGF-β1 during Langerhans cell differentiation and epidermal homeostasis

Autor: Nighat Yasmin, Susanne Richter, Jennifer Jurkin, Greg Lemke, Herbert Strobl, Bernhard Gesslbauer, René Köffel, Anna Zagórska, Thomas Bauer
Rok vydání: 2012
Předmět:
Keratinocytes
Mice
129 Strain
Langerhans cell
Cellular differentiation
Blotting
Western
Immunology
Gene Expression
Apoptosis
Dermatitis
Contact
Article
Receptor tyrosine kinase
Proinflammatory cytokine
Transforming Growth Factor beta1
Mice
03 medical and health sciences
0302 clinical medicine
Proto-Oncogene Proteins
Langerhans cell differentiation
medicine
Animals
Homeostasis
Humans
Immunology and Allergy
Cells
Cultured
030304 developmental biology
Mice
Knockout
0303 health sciences
AXL receptor tyrosine kinase
biology
Reverse Transcriptase Polymerase Chain Reaction
Cell growth
Gene Expression Profiling
Toll-Like Receptors
Receptor Protein-Tyrosine Kinases
Cell Differentiation
Axl Receptor Tyrosine Kinase
Cell biology
Mice
Inbred C57BL
medicine.anatomical_structure
Langerhans Cells
biology.protein
Intercellular Signaling Peptides and Proteins
Epidermis
Signal transduction
Signal Transduction
030215 immunology
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
Popis: Axl expression is induced by TGF-β1 during Langerhans cell differentiation and enhances apoptotic cell uptake and blocks proinflammatory cytokine production.
Transforming growth factor-β1 (TGF-β1) is a fundamental regulator of immune cell development and function. In this study, we investigated the effects of TGF-β1 on the differentiation of human Langerhans cells (LCs) and identified Axl as a key TGF-β1 effector. Axl belongs to the TAM (Tyro3, Axl, and Mer) receptor tyrosine kinase family, whose members function as inhibitors of innate inflammatory responses in dendritic cells and are essential to the prevention of lupus-like autoimmunity. We found that Axl expression is induced by TGF-β1 during LC differentiation and that LC precursors acquire Axl early during differentiation. We also describe prominent steady-state expression as well as inflammation-induced activation of Axl in human epidermal keratinocytes and LCs. TGF-β1–induced Axl enhances apoptotic cell (AC) uptake and blocks proinflammatory cytokine production. The antiinflammatory role of Axl in the skin is reflected in a marked impairment of the LC network preceding spontaneous skin inflammation in mutant mice that lack all three TAM receptors. Our findings highlight the importance of constitutive Axl expression to tolerogenic barrier immunity in the epidermis and define a mechanism by which TGF-β1 enables silent homeostatic clearing of ACs to maintain long-term self-tolerance.
Databáze: OpenAIRE
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