title: Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin.
abstract: We have investigated the efficacy of conditioning skin Langerhans cells (LCs) with agents to promote tolerance and reduce inflammation, with the goal of improving the outcomes of antigen-specific immunotherapy. Topical treatments were assessed ex vivo, using excised human breast skin maintained in organ bath cultures, and in vivo in healthy volunteers by analysing skin biopsies and epidermal blister roof samples. Following topical treatment with a corticosteroid, tumour necrosis factor-α levels were reduced in skin biopsy studies and blister fluid samples. Blister fluid concentrations of monocyte chemoattractant protein-1, macrophage inflammatory proteins -1α and 1β and interferon-γ inducible protein-10 were also reduced, while preserving levels of interleukin-1α (IL-1α), IL-6, IL-8 and IL-10. Steroid pre-treatment of the skin reduced the ability of LCs to induce proliferation, while supernatants showed an increase in the IL-10/interferon-γ ratio. Phenotypic changes following topical steroid treatment were also observed, including reduced expression of CD83 and CD86 in blister-derived LCs, but preservation of the tolerogenic signalling molecules immunoglobulin-like transcript 3 and programmed death-1. Reduced expression of HLA-DR, CD80 and CD86 were also apparent in LCs derived from excised human skin. Topical therapy with a vitamin D analogue (calcipotriol) and steroid, calcipotriol alone or vitamin A elicited no significant changes in the parameters studied. These experiments suggest that pre-conditioning the skin with topical corticosteroid can modulate LCs by blunting their pro-inflammatory signals and potentially enhancing tolerance. We suggest that such modulation before antigen-specific immunotherapy might provide an inexpensive and safe adjunct to current approaches to treat autoimmune diseases.
authors: Diabetes Research Group, Institute for Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
authors: Mohammad Alhadj
authors: MA
authors: Ali
authors: Weston General Hospital, Weston-super-Mare, UK.
authors: Sally L
authors: SL
authors: Thrower
authors: Diabetes Research Group, Institute for Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
authors: Stephanie J
authors: SJ
authors: Hanna
authors: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors: Sion A
authors: SA
authors: Coulman
authors: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors: James C
authors: JC
authors: Birchall
authors: Diabetes Research Group, Institute for Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
authors: F Susan
authors: FS
authors: Wong
authors: Diabetes Research Group, Institute for Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
authors: Colin Mark
authors: CM
authors: Dayan
authors: Diabetes Research Group, Institute for Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK.
authors: Danijela
authors: D
authors: Tatovic
mesh_terms: D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007165:Immunosuppression Therapy / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D066298:In Vitro Techniques; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D012333:RNA, Messenger; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone
keywords: human dendritic cells; skin; tolerance; topical steroid