Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin

Alhadj Ali, Mohammad ORCID: https://orcid.org/0000-0002-9780-6443, Thrower, Sally L., Hanna, Stephanie J., Coulman, Sion A. ORCID: https://orcid.org/0000-0002-1277-7584, Birchall, James C. ORCID: https://orcid.org/0000-0001-8521-6924, Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845, Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462 and Tatovic, Danijela ORCID: https://orcid.org/0000-0002-3879-2686 2015. Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin. Immunology 146 (3) , pp. 411-422. 10.1111/imm.12518

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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, TNF-α levels were reduced in skin biopsy studies and blister fluid samples. Blister fluid concentrations of MCP-1, MIP-1α, MIP-1β and IP-10 were also reduced, while preserving levels of IL-1α, IL-6, IL-8 and IL-10. Steroid pre-treatment of the skin reduced the ability of LCs to induce proliferation, whilst supernatants showed an increase in the IL-10/IFN-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 ILT3 and PD-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 prior to antigen specific immunotherapy might provide an inexpensive and safe adjunct to current approaches to treat autoimmune diseases.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	topical steroid; skin; human dendritic cells; tolerance
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License
Publisher:	Wiley
ISSN:	0019-2805
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	30 July 2015
Last Modified:	15 Aug 2024 08:44
URI:	https://orca.cardiff.ac.uk/id/eprint/76154

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