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PMID: 8976197 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: the skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells.

The Journal of experimental medicine ·Vol. 184 ·No. 6 ·1996-12-01 ·Pages 2417-22

Borkowski TA, Letterio JJ, Farr AG, Udey MC

Abstract

Transforming growth factor beta 1 (TGF-beta 1) regulates leukocytes and epithelial cells. To determine whether the pleiotropic effects of TGF-beta 1, 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-beta 1 null (TGF-beta 1 -/-) mice. I-A+ LC were not detected in epidermal cell suspensions or epidermal sheets prepared from TGF-beta 1 -/- mice, and epidermal cell suspensions were devoid of allostimulatory activity. In contrast, TCR-gamma delta + DETC were normal in number and appearance in TGF-beta 1 -/- mice and, importantly, DETC represented the only leukocytes in the epidermis. Immunolocalization studies revealed CD11c+ DC in lymph nodes from TGF-beta 1 -/- mice, although gp40+ DC were absent. Treatment of TGF-beta 1 -/- 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-beta 1 -/- 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-beta 1 is essential for normal murine LC development or epidermal localization.

MeSH Terms
Animals Cells, Cultured Coculture Techniques Female Flow Cytometry Immunosuppressive Agents/pharmacology Langerhans Cells/cytology,immunology Lymph Nodes/immunology Mice Mice, Inbred BALB C Mice, Knockout Phenotype Polyenes/pharmacology Sirolimus Skin/cytology,immunology T-Lymphocytes/immunology Transforming Growth Factor beta/deficiency,genetics,physiology
Chemicals
Immunosuppressive Agents Polyenes Transforming Growth Factor beta Sirolimus
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Borkowski T A
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1908, USA.
Letterio J J
Farr A G
Udey M C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.6.2417
Published
1996-12-01
Pages
2417-22
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196398
Subset
IM
Grants
NIA NIH HHS · AG 04350 · United States
NIAID NIH HHS · AI 24137 · United States
External Links
PubMed source DOI: 10.1084/jem.184.6.2417 PMC Full Text View journal details
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