title: Regulation of tumor antigen presentation by urocanic acid.
abstract: Urocanic acid (UCA) accumulates in the epidermis after deamination of histidine. UCA isomerizes from the trans to the cis form upon exposure to environmental UV radiation. Cis-UCA is immunosuppressive in several models. Topically applied cis-UCA was reported to enhance the cutaneous tumor yield in chronically UV-irradiated mice, suggesting involvement of cis-UCA in photocarcinogenesis. Since Langerhans cells (LC) are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor-immune responses, we examined the effects of trans- and cis-UCA on LC tumor Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). In this system, induction of immunity requires exposure of LC to granulocyte-macrophage CSF. Naive CAF1 (H-2(a/d)) mice were immunized against S1509a by injection with granulocyte-macrophage CSF-exposed and TAA-pulsed epidermal cells (EC), as assessed by growth inhibition of inoculated tumor cells. Incubation of EC in cis-, but not trans-UCA completely inhibited Ag presentation in this system. Neither histamine antagonists nor indomethacin reversed these effects of cis-UCA. The ability of trans- and cis-UCA to modulate EC presentation of TAA for secondary immune responses was also examined. EC were pulsed with TAA in vitro and then injected into hind footpads of tumor-immune mice. After 24 h, footpad swelling was assessed as a measure of delayed-type hypersensitivity. Incubation with cis-, but again not trans-UCA before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity. These data indicate that cis-UCA may be an important regulator of LC Ag-presenting function in tumor-immune responses, and thus may play a role in photocarcinogenesis.
authors.affiliation: MGH/Harvard Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital-East and Harvard Medical School, Charlestown 02129, USA. beisser@uni-muenster.de
authors.forename: S
authors.initials: S
authors.lastname: Beissert
authors.forename: T
authors.initials: T
authors.lastname: Mohammad
authors.forename: H
authors.initials: H
authors.lastname: Torri
authors.forename: A
authors.initials: A
authors.lastname: Lonati
authors.forename: Z
authors.initials: Z
authors.lastname: Yan
authors.forename: H
authors.initials: H
authors.lastname: Morrison
authors.forename: R D
authors.initials: RD
authors.lastname: Granstein
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology*; D013237:Stereoisomerism; D014560:Urocanic Acid / Q000737:chemistry / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D014560:Urocanic Acid