| First Author | Mohammed J | Year | 2013 |
| Journal | J Invest Dermatol | Volume | 133 |
| Issue | 1 | Pages | 135-43 |
| PubMed ID | 22832490 | Mgi Jnum | J:196492 |
| Mgi Id | MGI:5488574 | Doi | 10.1038/jid.2012.241 |
| Citation | Mohammed J, et al. (2013) TGFbeta1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity. J Invest Dermatol 133(1):135-43 |
| abstractText | Overexpression of transforming growth factor beta-1 (TGFbeta1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGFbeta1 overproduction by keratinocytes on skin dendritic cells (DCs). TGFbeta1 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 TGFbeta1-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 TGFbeta1 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 TGFbeta1 overexpression in skin explants and by exogenous TGFbeta1 in culture media. Transient TGFbeta1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGFbeta1 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 TGFbeta1 in DC trafficking and in the initiation of skin inflammation. |
