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

DH Kaplan, MO Li, MC Jenison… - Journal of Experimental …, 2007 - rupress.org
DH Kaplan, MO Li, MC Jenison, WD Shlomchik, RA Flavell, MJ Shlomchik
Journal of Experimental Medicine, 2007rupress.org
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 TGF ß1 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 TGF ß1 is uncertain because BM
chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGF …
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 TGF ß1 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 TGF ß1 is uncertain because BM chimera experiments showed that neither hematopoietic nor nonhematopoietic-derived TGF ß1 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 TGF ßRII and TGF ß1 mice, thereby generating mice with LCs that either cannot respond to or generate TGF ß1, respectively. Langerin-Cre TGF ßRII mice had substantially reduced numbers of epidermal LCs, demonstrating that TGF ß1 acts directly on LCs in vivo. Interestingly, Langerin-Cre TGF ß1 mice also had very few LCs both in the steady state and after BM transplantation. Thus, TGF ß1 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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