TGF-beta/Smad pathway is not required for epidermal LC development
Xu Y, Li G, Huang T, Zhou L, Mi Q. TGF-beta/Smad pathway is not required for epidermal LC development. Journal of Investigative Dermatology 2018; 138(5 Suppl S):S175.
Journal of Investigative Dermatology
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 tested LC number and maturation in conventional Smad3KO mice, there were no differences between mutant and WT mice. Given that the function of Smad2 and Smad4 might be redundance, we further investigated the effect of deletion of individual Smad2 or Smad4 on LCs, and found both of them did not significantly affect LC ratios in skin and their expression of MHC-II, CD80 and CD86 in both models. Furthermore, we crossed CSF1R-Cre and hLangerin-Cre transgenic mice with Smad2fl/fland 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 both Smad2 and Smad4 in LCs also had no effect on LC number, maturation and phagocytic ability in Smad2/4 double KO mice induced by CSF1Rcre compared to that of 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.
5 Suppl S