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Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin
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 o...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610630/ https://www.ncbi.nlm.nih.gov/pubmed/26293297 http://dx.doi.org/10.1111/imm.12518 |
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author | Alhadj Ali, Mohammad Thrower, Sally L Hanna, Stephanie J Coulman, Sion A Birchall, James C Wong, F Susan Dayan, Colin Mark Tatovic, Danijela |
author_facet | Alhadj Ali, Mohammad Thrower, Sally L Hanna, Stephanie J Coulman, Sion A Birchall, James C Wong, F Susan Dayan, Colin Mark Tatovic, Danijela |
author_sort | Alhadj Ali, Mohammad |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4610630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley & Sons, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-46106302016-11-01 Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin Alhadj Ali, Mohammad Thrower, Sally L Hanna, Stephanie J Coulman, Sion A Birchall, James C Wong, F Susan Dayan, Colin Mark Tatovic, Danijela Immunology Original Articles 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. John Wiley & Sons, Ltd 2015-11 2015-09-13 /pmc/articles/PMC4610630/ /pubmed/26293297 http://dx.doi.org/10.1111/imm.12518 Text en © 2015 The Authors. Immunology published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Alhadj Ali, Mohammad Thrower, Sally L Hanna, Stephanie J Coulman, Sion A Birchall, James C Wong, F Susan Dayan, Colin Mark Tatovic, Danijela Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin |
title | Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin |
title_full | Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin |
title_fullStr | Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin |
title_full_unstemmed | Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin |
title_short | Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin |
title_sort | topical steroid therapy induces pro-tolerogenic changes in langerhans cells in human skin |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610630/ https://www.ncbi.nlm.nih.gov/pubmed/26293297 http://dx.doi.org/10.1111/imm.12518 |
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