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Topical steroid therapy induces pro‐tolerogenic changes in Langerhans cells in human skin
Author(s) -
Alhadj Ali Mohammad,
Thrower Sally L.,
Hanna Stephanie J.,
Coulman Sion A.,
Birchall James C.,
Wong F Susan,
Dayan Colin Mark,
Tatovic Danijela
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12518
Subject(s) - calcipotriol , medicine , immunotherapy , langerhans cell , cd80 , cytokine , immunology , human skin , tumor necrosis factor alpha , cd86 , monocyte , inflammation , topical steroid , pharmacology , antigen , immune system , biology , t cell , psoriasis , in vitro , cd40 , cytotoxic t cell , biochemistry , genetics
Summary We have investigated the efficacy of conditioning skin Langerhans cells ( LC s) 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 ‐1 α and 1 β and interferon‐ γ inducible protein‐10 were also reduced, while preserving levels of interleukin‐1 α ( IL ‐1 α ), IL ‐6, IL ‐8 and IL ‐10. Steroid pre‐treatment of the skin reduced the ability of LC s 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 CD 83 and CD 86 in blister‐derived LC s, but preservation of the tolerogenic signalling molecules immunoglobulin‐like transcript 3 and programmed death‐1. Reduced expression of HLA ‐ DR , CD 80 and CD 86 were also apparent in LC s 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 LC s 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.