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7318331 
Journal Article 
Effect of oral eicosapentaenoic acid on epidermal Langerhans cell numbers and PGD2 production in UVR-exposed human skin: a randomised controlled study 
Pilkington, SM; Gibbs, NK; Costello, P; Bennett, SP; Massey, KA; Friedmann, PS; Nicolaou, A; Rhodes, LE 
2016 
1 
Experimental Dermatology
ISSN: 0906-6705
EISSN: 1600-0625 
Blackwell Publishing Ltd 
25 
12 
962-968 
English 
27572109 
WOS:000388647200007 
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/mm2 from 913 (28) to 322 (40) (P<.001), and mean PGD2 level 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, PGD2 or 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 PGD2 levels in humans, starkly contrasting with reported effects of UVR on other skin PG. Lowered PGD2 levels could reflect LC loss from the epidermis and/or altered dendritic cell activity and may be relevant for phototherapy of skin disease. 
dendritic cells; Omega-3 fatty acids; photoimmunosuppression; prostaglandin D2; systemic photoprotection; gamma interferon; icosapentaenoic acid; interleukin 10; interleukin 17; interleukin 1beta; interleukin 23; interleukin 4; interleukin 8; prostaglandin D2; tumor necrosis factor; 9-deoxy-delta-9-prostaglandin D2; cytokine; icosapentaenoic acid; prostaglandin D2; adult; animal experiment; Article; bioavailability; blister; blister fluid; cell count; cellular immunity; controlled study; double blind procedure; drug effect; erythrocyte; female; human; human tissue; immunofluorescence; immunomodulation; Langerhans cell; liquid chromatography; mouse; nonhuman; photoimmunosuppression; radiation exposure; randomized controlled trial; sampling; skin; supplementation; tandem mass spectrometry; ultraviolet radiation; analogs and derivatives; dietary supplement; drug effects; immunological tolerance; immunology; Langerhans cell; metabolism; middle aged; radiation response; ultraviolet radiation; young adult; Adult; Cytokines; Dietary Supplements; Double-Blind Method; Eicosapentaenoic Acid; Female; Humans; Immune Tolerance; Langerhans Cells; Middle Aged; Prostaglandin D2; Skin; Ultraviolet Rays; Young Adult