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.
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.
Borkowski
T A
TA
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1908, USA.
Letterio
J J
JJ
Farr
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AG
Udey
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MC
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010641:Phenotype; D011090:Polyenes / Q000494:pharmacology; D020123:Sirolimus; D012867:Skin / Q000166:cytology* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*
D007166:Immunosuppressive Agents; D011090:Polyenes; D016212:Transforming Growth Factor beta; D020123:Sirolimus