title: Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2production in UVR-exposed human skin: a randomised controlled study.
abstract: Langerhans cells (LCs) are sentinels of skin's immune system, their loss from epidermis contributing to UVR suppression of cell-mediated immunity (CMI). Omega-3 polyunsaturated fatty acids show potential to reduce UVR suppression of CMI in mice and humans, potentially through modulation of LC migration. Our objectives were to examine whether eicosapentaenoic acid (EPA) ingestion influences UV-mediated effects on epidermal LC numbers and levels of immunomodulatory mediators including prostaglandin (PG)D2, which is expressed by LC. In a double-blind randomised controlled study, healthy individuals took 5-g EPA-rich (n=40) or control (n=33) lipid for 12 weeks; UVR-exposed and unexposed skin samples were taken pre- and postsupplementation. Epidermal LC numbers were assessed by immunofluorescence for CD1a, and skin blister fluid PG and cytokines were quantified by LC-MS/MS and Luminex assay, respectively. Presupplementation, UVR reduced mean (SEM) LC number/mm2from 913 (28) to 322 (40) (P<.001), and mean PGD2level by 37% from 8.1 (11.6) to 5.1 (5.6) pg/μL; P<.001), while IL-8 level increased (P<.001). Despite confirmation of EPA bioavailability in red blood cells and skin in the active group, no between-group effect of EPA was found on UVR modulation of LC numbers, PGD2or cytokine levels postsupplementation. Thus, no evidence was found for EPA reduction of photoimmunosuppression through an impact on epidermal LC numbers. Intriguingly, UVR exposure substantially reduced cutaneous PGD2levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD2levels could reflect LC loss from the epidermis and/or altered dendritic cell activity and may be relevant for phototherapy of skin disease.
authors: Centre for Dermatology, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors: Suzanne M
authors: SM
authors: Pilkington
authors: Centre for Dermatology, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors: Neil K
authors: NK
authors: Gibbs
authors: Centre for Dermatology, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors: Patrick
authors: P
authors: Costello
authors: Centre for Dermatology, Salford Royal Hospital, Manchester Academic Health Science Centre, Manchester, UK.
authors: Susan P
authors: SP
authors: Bennett
authors: School of Pharmacy, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors: Karen A
authors: KA
authors: Massey
authors: Faculty of Medicine, University of Southampton, Southampton, UK.
authors: Peter S
authors: PS
authors: Friedmann
authors: School of Pharmacy, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors: Anna
authors: A
authors: Nicolaou
authors: Centre for Dermatology, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.|Centre for Dermatology, Salford Royal Hospital, Manchester Academic Health Science Centre, Manchester, UK.
authors: Lesley E
authors: LE
authors: Rhodes
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007801:Langerhans Cells / Q000187:drug effects*; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D016207:Cytokines; C037112:9-deoxy-delta-9-prostaglandin D2; D015118:Eicosapentaenoic Acid; D015230:Prostaglandin D2
keywords: Omega-3 fatty acids; dendritic cells; photoimmunosuppression; prostaglandin D2; systemic photoprotection