TGFβ/Smad2/4 Signaling Pathway Is Required for Epidermal Langerhans Cell Repopulation Under Inflammation Condition but Not for Their Homeostasis, Maturation and Migration in the Steady State
Cvetkovski S, Huang L, Li G, Xu Y, Udo-Inyang I, Yin C, Zhou L, Yao Z, and Mi Q. TGFβ/Smad2/4 Signaling Pathway Is Required for Epidermal Langerhans Cell Repopulation Under Inflammation Condition but Not for Their Homeostasis, Maturation and Migration in the Steady State J Invest Dermatol 2019; 139(9):B2.
J Invest Dermatol
Langerhans cells (LC) represent a specialized subset of evolutionarily conserved dendritic cells (DC) in skin, which are essential for induction of skin immunity and tolerance. They self-renew in the skin at steady state, but could repopulate from peripheral blood Gr-1hi monocytes and bone marrow (BM) hematopoietic stem cells at inflammatory state. Transforming growth factor-beta1 (TGFβ1) is a crucial factor in the regulation of LC maintenance and function after birth, however the underlying TGFβ signaling pathways are still unclear. We previously reported that the TGFβ/Smad3 signaling pathway does not impact LC homeostasis and their functions. Here, we generated the mice with conditional deletion of Smad2 or Smad4 in LCs to further explore the role of TGFβ/Smad2/4 signaling pathway in LC maintenance and function. We found that deletion of individual Smad2 or Smad4, or Smad2/4 together, in LCs did not significantly affect their ratios in skin and their expression of MHC-II, CD80 and CD86 at steady state. The phagocytic capacity of LCs from all 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 upregulated on LCs between KO and WT mice. Surprisingly, we found that conditional deletion of Smad2 and Smad4 in LCs leads to a conspicuous interruption of BM-derived LC repopulation during inflammation. Overall, our data suggest that conventional TGF-β/Smad2/3/4 signaling pathways are not required for maintaining LC homeostasis and the immature stage in the epidermis as well as LC maturation upon stimulation, but required for LC repopulation in inflammatory conditions.