title: Neural influences on induction of contact hypersensitivity.
abstract: Contact hypersensitivity (CH)-induction begins when cutaneous antigen-presenting cells (APC) capture hapten that has been applied epicutaneously, and the process prepares hapten for presentation to T-cells. APCs are functionally plastic, are influenced by the microenvironment in which they reside, and their functional properties have a profound effect on the phenotype of the hapten-specific T-cells that they activate. Ultraviolet B radiation (UVR) distorts the cutaneous microenvironment, thereby altering local APC function, and changing the immune outcome from sensitization to unresponsiveness. Although UVR induces keratinocytes to produce TNF alpha and IL-10 (cytokines that have been implicated in failed CH-induction and tolerance, respectively, after UVR), dermal mast cells turn out to be the source of these immunomodulatory cytokines. Mast cell degranulation is triggered by CGRP released from UVR-exposed cutaneous nerve termini. Even in normal skin, cutaneous nerves influence the immune response to haptens. Substance P released from cutaneous nerves acts as an adjuvant, raising the immunogenicity of epicutaneously applied haptens. Thus, the nerves and the neuropeptides that these processes release contribute to the cutaneous microenvironment. By altering APC function, cutaneous nerves can dictate the quality and the quantity of immune responses to antigens of the skin.
authors.affiliation: Schepens Eye Research Institute, Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Streilein
authors.forename: P
authors.initials: P
authors.lastname: Alard
authors.forename: H
authors.initials: H
authors.lastname: Niizeki
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D003877:Dermatitis, Contact / Q000503:physiopathology*; D006801:Humans; D015603:Keratinocytes / Q000276:immunology / Q000528:radiation effects; D015213:Neuroimmunomodulation / Q000502:physiology*; D012867:Skin / Q000276:immunology* / Q000294:innervation*; D014466:Ultraviolet Rays
chemical_list: D016207:Cytokines