The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20071401
The Journal of Experimental Medicine, Vol. 204, No. 11, 2545-2552
The Rockefeller University Press, 0022-1007 $30.00
© Kaplan et al.
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BRIEF DEFINITIVE REPORT

 Autocrine/paracrine TGFß1 is required for the development of epidermal Langerhans cells

Daniel H. Kaplan1, Ming O. Li3, Matthew C. Jenison1, Warren D. Shlomchik3,4, Richard A. Flavell3, and Mark J. Shlomchik2,3

1 Department of Dermatology, 2 Department of Laboratory Medicine, 3 Section of Immunobiology, and 4 Section of Medical Oncology, Yale University School of Medicine, New Haven, CT 06520

CORRESPONDENCE Daniel H. Kaplan: dankaplan{at}umn.edu

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) ß1-deficient mice. It is not clear whether TGFß1 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 TGFß1 is uncertain because BM chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGFß1 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 TGFßRII and TGFß1 mice, thereby generating mice with LCs that either cannot respond to or generate TGFß1, respectively. Langerin-Cre TGFßRII mice had substantially reduced numbers of epidermal LCs, demonstrating that TGFß1 acts directly on LCs in vivo. Interestingly, Langerin-Cre TGFß1 mice also had very few LCs both in the steady state and after BM transplantation. Thus, TGFß1 derived from LCs acts directly on LCs through an autocrine/paracrine loop, and it is required for LC development and/or survival.

Abbreviations used: BAC, bacterial artificial chromosome; CSF, colony-stimulating factor; EGFP, enhanced GFP; HSC, hematopoietic stem cell; LC, Langerhans cell.


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