TGF?1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity.

ABSTRACT: Overexpression of transforming growth factor beta-1 (TGF?1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGF?1 overproduction by keratinocytes on skin dendritic cells (DCs). TGF?1 induction for 2 and 4 days increased the numbers and CD86 expression of B220(+) plasmacytoid DCs (pDCs) and CD207(+)CD103(+), CD207(-)CD103(-)CD11b(+), and CD207(-)CD103(-)CD11b(-) dermal DCs (dDCs) in skin-draining lymph nodes (SDLNs). The dermis of TGF?1-overexpressing mice had significantly more pDCs, CD207(+)CD103(+) dDCs, and CD207(-)CD11b(+) dDCs in the absence of increased dermal proliferation. Application of dye, tetramethyl rhodamine iso-thiocyanate (TRITC), in dibutylpthalate (DBP) solution after TGF?1 induction increased the numbers of TRITC(+)CD207(-) dDCs in SDLNs, and augmented TRITC/DBP-induced Langerhans cell (LC) migration 72 ?hours post TRITC treatment. Consistent with this, LC migration was increased in vitro by TGF?1 overexpression in skin explants and by exogenous TGF?1 in culture media. Transient TGF?1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGF?1 alone is sufficient to alter homeostasis of multiple cutaneous DC subsets, and enhance DC migration and immune responses to contact sensitizers. These results highlight a role for keratinocyte-derived TGF?1 in DC trafficking and in the initiation of skin inflammation.

SUBMITTER: Mohammed J 

PROVIDER: S-EPMC3491121 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature