NDLI: TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Reizis, Boris Kel, Junda M. Girard-Madoux, Mathilde J. H. Clausen, Björn E.
Description	Country affiliation: Netherlands Author Affiliation: Kel JM ( Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.)
Abstract	The pivotal role of TGF-beta in Langerhans cell (LC) development has been previously established in TGF-beta-deficient mice, which lack epidermal LCs. As to whether TGF-beta also governs LC homeostasis and function remains elusive. To assess the role of TGF-beta-mediated control of cutaneous dendritic cells (DCs) in vivo, we generated mice with a conditional knockout of the TGF-beta receptor 1 (TbetaR1) under a DC-specific promoter (DC-TbetaR1(del) mice). While initial LC seeding occurred in DC-TbetaR1(del) mice, the cells disappeared from the epidermis during the first week of life. TbetaR1-deficient LCs demonstrated spontaneous maturation and gained migratory potential based on increased surface expression of MHC class II, costimulatory molecules, and CCR7 and downregulation of E-cadherin. In parallel to their early loss from the epidermis, migrating LCs were reduced in the dermis and skin-draining lymph nodes of adult DC-TbetaR1(del) mice, whereas the number of Langerin(+) dermal DCs was similar to wild-type. In the absence of LCs, low-dose contact hypersensitivity in DC-TbetaR1(del) mice was significantly diminished. In contrast, ear swelling was restored to wild-type levels when a higher hapten dose was applied to efficiently target TbetaR1-deficient dermal DCs. In conclusion, TGF-beta inhibits in vivo LC maturation and migratory phenotype, identifying TGF-beta as a critical factor controlling LC homeostasis in the steady state.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	185
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2010-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Differentiation Immunology Epidermis Cytology Langerhans Cells Transforming Growth Factor Beta1 Physiology Animals Genetics Cell Movement Cells, Cultured Dermatitis, Contact Metabolism Pathology Homeostasis Mice Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Protein-serine-threonine Kinases Deficiency Receptors, Transforming Growth Factor Beta Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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