Relevance of Langerhans Cells in skin inflammation

NICOLÁS PINTO; GABRIEL A. RABINOVICH; CERLIANI J. P.

Workshop; 14th International Workshop on Langerhans Cells; 2015

Epidermis contains several specialized cells that have specific roles in immune response, including lymphocytes and Langerhans Cells (epidermal dendritic cells (LCs CD207+CD11b+CD205+). These cells remain anchored to keratinocytes through E-Cadherin specific interactions. However, when they are exposed to a stimulus, LCs down-regulate E-Cadherin acquiring a mesenchymal phenotype. This process promotes LCs deattachment from keratinocytes and gain the ability to migrate towards a skin draining lymph node where they interact with CD4+ T cells. It was described that in inflammatory conditions LCs polarize T cell response towards Th1 and TH17 phenotype. However, depletion of LCs in mouse inflammatory skin models has shown an augmented in inflammatory clinical score. In others works, some authors have demonstrated that LCs does not participates in inflammatory response. In this sense, whether LCs orchestrates an inflammatory or regulatory immune response remains unclear. Based on this background, the aim of this work is to elucidate the relevance of LCs towards T cell polarization in the skin immune system during the development of different inflammatory disorders. First, we performed a psoriasis-induced protocol in which CD207-DTR-GFP mice were topical treated during one week with Imiquimod We observed that LCs-depleted mice (single diphtheria toxin injection (1ug/ml i.p.), decrease the total number of Treg cells in theirs epidermis, skin draining lymph nodes and spleen as compared with CD207-DTR-GFP control mice (injected with diphtheria toxin vehicle). In addition, LCs-depleted mice also showed an increase in CD8+ T cells in the spleen as compared to control mice. Secondly, we performed an irritant dermatitis mouse model for three days by the topical application of TPA in CD207-DTR-GFP mice. LCs-depleted mice showed an increase in skin ear swelling as compared with control mice. These mice also showed an augmented CD8+ T cells skin infiltrate and decreased epidermal Treg cells than control mice.In conclusion, our results suggest that LCs promotes a tolerogenic microenvironment in the skin favoring a T cell regulatory profile that attenuates skin inflammation and decreases inflammatory cellular infiltrate.