TGFβ1 promotes adaptive immune response by modulating skin dendritic cell function and migration (147.24)

Abstract

Abstract TGFβ1 is required for the development of Langerhans cell (LC) in the skin as TGFβ1 null mice are devoid of any LC’s. While autocrine or paracrine effects of TGFβ1 have been studied in cell-specific TGFβ1 or TGFβ1RII knockout mouse models, little information is available on effects of TGFβ1 overexpression in LC function. We overexpressed active TGFβ1 in keratinocytes and monitored the paracrine effects on skin antigen presenting cell (APC) migration in vitro and in vivo. There was an increase in migration of MHC II+CD11c+ cells from ear skin following TGFβ1 overexpression by keratinocytes and a significant increase in APC migration following treatment of mouse ear skin explant with exogenous TGFβ1. Analysis of epidermal sheets following 5 days of TGFβ1 overexpression in vivo suggested an activated phenotype of APC with loss of typical dendritic morphology and increase in MHC II staining. There was enhancement in migration of skin APC’s to the skin draining lymph nodes following application of a hapten to TGFβ1 overexpressing skin. Induction of TGFβ1 in the skin 24 hrs prior to sensitization with 0.5% Dinitro-fluorobenzene resulted in increased inflammation following challenge. These results suggest that paracrine effects of TGFβ1 promote activation and migration of skin APC’s thereby enhancing skin adaptive immune response.