TGF-β1 regulates epidermal LCs in a Smad-independent pathway
Huang L, Li GH. TGF-β1 regulates epidermal LCs in a Smad-independent pathway. J Immunol 2018; 200(1).
Transforming growth factor-β1 (TGF-β1) is a key factor for Langerhans cell (LC) homeostasis and maintaining in the epidermis, but the underlying mechanisms in TGF-β signaling pathways remain elusive. Canonically, binding of TGF-β to TGF-βR activates Smad2 or Smad3, which subsequently heterodimerizes with Smad4 and then translocates into the nucleus acting as transcriptional regulators of TGF-β1 target genes. In order to investigate if Smad-dependent pathways are required for epidermal LC maintenance, we first crossed CSF1R-Cre and hLangerin-Cre transgenic mice with Smad2fl/fl and Smad4fl/fl, mice to generate the mutant mice with conditional Smad2 and Smad4 deletion at birth (CSF1Rcre) or 3 days after birth (hlangerinCre). Surprisingly, deletion of individual Smad2 or Smad4 in LCs did not significantly affect their ratios in skin and their expression of MHC-II, CD80 and CD86 in both models. The phagocytic capacity of LCs from KO mice was unaltered in vivo and in vitro compared to WT LCs. Furthermore, upon in vitro stimulation, MHC-II, CD80 and CD86 were comparably unregulated on LCs between KO and WT mice. We further tested LC number and maturation in conventional Smad3KO mice as well as Smad2/4 double KO mice induced by CSF1Rcre, the number and maturation of LCs are comparable between mutant and WT mice. Overall, our data suggest that conventional TGF-β/Smad2/3/4 signaling pathways may not be required for maintaining LC homeostasis and immature stage in the epidermis and LC maturation upon stimulation. The underlying mechanisms that Smad2/3/4-independent TGF-β pathways involved in LC maintenance and function remain to be further determined.
Copyright © 2018 by The American Association of Immunologists, Inc.