A Role for Endogenous Transforming Growth Factor β1 in Langerhans Cell Biology: The Skin of Transforming Growth Factor β1 Null Mice Is Devoid of Epidermal Langerhans Cells
Abstract
Transforming growth factor β1 (TGF-β1) regulates leukocytes and epithelial cells. To determine whether the pleiotropic effects of TGF-β1, a cytokine that is produced by both keratinocytes and Langerhans cells (LC), extend to epidermal leukocytes, we characterized LC (the epidermal contingent of the dendritic cell [DC] lineage) and dendritic epidermal T cells (DETC) in TGF-β1 null (TGF-β1 −/−) mice. I-A+ LC were not detected in epidermal cell suspensions or epidermal sheets prepared from TGF-β1 −/− mice, and epidermal cell suspensions were devoid of allostimulatory activity. In contrast, TCR-γδ+ DETC were normal in number and appearance in TGF-β1 −/− mice and, importantly, DETC represented the only leukocytes in the epidermis. Immunolocalization studies revealed CD11c+ DC in lymph nodes from TGF-β1 −/− mice, although gp40+ DC were absent. Treatment of TGF-β1 −/− mice with rapamycin abrogated the characteristic inflammatory wasting syndrome and prolonged survival indefinitely, but did not result in population of the epidermis with LC. Thus, the LC abnormality in TGF-β1 −/− mice is not a consequence of inflammation in skin or other organs, and LC development is not simply delayed in these animals. We conclude that endogenous TGF-β1 is essential for normal murine LC development or epidermal localization.
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Endogenous TGF-β1 is essential for normal murine Langerhans cell development and TGF-β1 acts directly on Langerhans cells through an autocrine/paracrine loop.
“it has been reported that endogenous TGF-β1 is essential for normal murine Langerhans cell development35 and TGF-β1 acts directly on Langerhans cells through an autocrine/paracrine loop36.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [35]
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- Authors
- Borkowski, T. A., Letterio, J. J., Farr, A. G., & Udey, M. C.
- Affiliations
- From the *Dermatology Branch and ‡the Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1908; and the §Department of Biological Structure, University of Washington, Seattle, Washington 98195
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1996-12-01
- Volume
- 184
- Issue
- 6
- Pages
- 2417-2422
- ISSN
- 0022-1007
- 1540-9538
- PMC
- PMC2196398
- Cited by
- 402
- References
- 0
- Language
- en
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