title: TGFβ1 overexpression by keratinocytes alters skin dendritic cell homeostasis and enhances contact hypersensitivity.
abstract: Overexpression of transforming growth factor beta-1 (TGFβ1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGFβ1 overproduction by keratinocytes on skin dendritic cells (DCs). TGFβ1 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 TGFβ1-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 TGFβ1 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 TGFβ1 overexpression in skin explants and by exogenous TGFβ1 in culture media. Transient TGFβ1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGFβ1 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 TGFβ1 in DC trafficking and in the initiation of skin inflammation.
authors: Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, PA, USA.
authors: Javed
authors: J
authors: Mohammed
authors: Andrew J
authors: AJ
authors: Gunderson
authors: Hong-Hanh
authors: HH
authors: Khong
authors: Richard D
authors: RD
authors: Koubek
authors: Mark C
authors: MC
authors: Udey
authors: Adam B
authors: AB
authors: Glick
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003877:Dermatitis, Contact / Q000378:metabolism*; D020405:Dermis / Q000187:drug effects / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000008:administration & dosage; D005260:Female; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D007801:Langerhans Cells / Q000187:drug effects / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D012235:Rhodamines / Q000008:administration & dosage; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D012235:Rhodamines; D053773:Transforming Growth Factor beta1; D003993:Dibutyl Phthalate; C009434:tetramethylrhodamine isothiocyanate; D017493:Leukocyte Common Antigens