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.

Treatment with silver nitrate versus topical steroid treatment for umbilical granuloma: A non-inferiority randomized control trial

“…In terms of the pathological mechanisms, glucocorticosteroids are known to suppress immune pathways in keratinocytes and to negatively affect the viability, maturation, and immune function of inflammatory cells [ 17 , 18 ]. In addition, recent findings have shown that topical steroids may achieve anti-inflammatory effects and contribute to reduced numbers of fibroblasts [ 19 , 20 ]. The lesion in UG is characterized by overgrowth of granulation tissue after umbilical cord separation.…”

Synergistic Effect of H1-Antihistamines on Topical Corticosteroids for Pruritus in Atopic Dermatitis: A Systematic Review and Meta-Analysis

“…Topical steroid therapy can modulate the Langerhans cells in the human skin through inhibiting proinflammatory signals and enhancing tolerance 18 . For example, cytokines, such as TNF-α and IL-1β, have been reported to decrease on the ocular surface following application of topical steroids 19 .…”

Immune System Remodelling by Prenatal Betamethasone: Effects on β-Cells and Type 1 Diabetes

“…Furthermore, the release of proinflammatory cytokines was reduced by this drug in DCs. Betamethasone has been reported to induce tolerogenic Langerhans DCs (LDCs) in the skin of patients with psoriasis ( 47 ) and atopic dermatitis, which in turn arrest T helper (Th) 1 and Th2 responses ( 48 ). Similarly to the effects found in monocytes, human DCs differentiated with betamethasone showed a reduction of membrane expression of costimulatory molecules, such as CD40 and CD86, accompanied by a decrease in IL-12 secretion, an important cytokine for Th1 responses.…”