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Autocrine/paracrine TGFβ1 is required for the development of epidermal Langerhans cells

Kaplan, Daniel H., Li, Ming O., Jenison, Matthew C., Shlomchik, Warren D., Flavell, Richard A., Shlomchik, Mark J.·2007·The Journal of Experimental Medicine
DOI 10.1084/jem.20071401PMC PMC2118472
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Abstract

Langerhans cells (LCs) are bone marrow (BM)–derived epidermal dendritic cells (DCs) that develop from precursors found in the dermis. Epidermal LCs are absent in transforming growth factor (TGF) β1-deficient mice. It is not clear whether TGFβ1 acts directly on LC precursors to promote maturation or whether it acts on accessory cells, which in turn affect LC precursors. In addition, the physiologic source of TGFβ1 is uncertain because BM chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGFβ1 is required for LC development. To address these issues, we created mice transgenic for a bacterial artificial chromosome (BAC) containing the gene for human Langerin into which Cre recombinase had been inserted by homologous recombination (Langerin-Cre). These mice express Cre selectively in LCs, and they were bred to floxed TGFβRII and TGFβ1 mice, thereby generating mice with LCs that either cannot respond to or generate TGFβ1, respectively. Langerin-Cre TGFβRII mice had substantially reduced numbers of epidermal LCs, demonstrating that TGFβ1 acts directly on LCs in vivo. Interestingly, Langerin-Cre TGFβ1 mice also had very few LCs both in the steady state and after BM transplantation. Thus, TGFβ1 derived from LCs acts directly on LCs through an autocrine/paracrine loop, and it is required for LC development and/or survival.

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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 [36]

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Authors
Kaplan, D. H., Li, M. O., Jenison, M. C., Shlomchik, W. D., Flavell, R. A., & Shlomchik, M. J.
Affiliations
  • 1Department of Dermatology
  • 3Section of Immunobiology,
  • 2Department of Laboratory Medicine
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2007-10-15
Volume
204
Issue
11
Pages
2545-2552
ISSN
  • 1540-9538
  • 0022-1007
DOI
10.1084/jem.20071401
PMC
PMC2118472
Cited by
239
References
0
Language
en

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