Impact of house dust mite in vitiligo skin: environmental contribution to increased cutaneous immunity and melanocyte detachment

Abstract

Background Vitiligo is an autoimmune skin disorder characterized by loss of melanocytes. Protease-mediated disruption of junctions between keratinocytes and/or keratinocyte intrinsic dysfunction may directly contribute to melanocyte loss. House dust mite (HDM), an environmental allergen with potent protease activity, contributes to respiratory and gut disease but also to atopic dermatitis and rosacea. Objective To verify if HDM can contribute to melanocyte detachment in vitiligo and if so, by which mechanism(s). Methods Using primary human keratinocytes, human skin biopsies from healthy and vitiligo patients, and 3D reconstructed human epidermis, we studied the effect of HDM on cutaneous immunity, tight and adherent junction expression and melanocyte detachment. Results HDM increased keratinocyte production of vitiligo-associated cytokines and chemokines and increased expression of TLR-4. This was associated with increased in situ MMP-9 activity, reduced cutaneous expression of adherent protein E-cadherin, increased soluble E-cadherin in culture supernatant and significantly increased number of supra-basal melanocytes in the skin. This effect was dose-dependent and driven by cysteine protease Der p1 and MMP-9. Selective MMP-9 inhibitor, Ab142180 restored E-cadherin expression and inhibited HDM-induced melanocyte detachment. Keratinocytes from vitiligo patients were more sensitive to HDM-induced changes than healthy keratinocytes. All results were confirmed in 3D model of healthy skin and in human skin biopsies. Conclusions Our results highlight that environmental mite may act as an external source of PAMPs in vitiligo and topical MMP-9 inhibitors may be useful therapeutic targets. Whether HDM contributes to onset of flares in vitiligo remains to be tested in carefully controlled trials.

Human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium

“…SE-Cad and SN-Cad have different functions compared to the full-length Cadherin. Nevertheless, in different cells types and tissues such as in endothelial cells, keratinocytes, pulmonary fibrosis, tumor, and inflammatory diseases, both SE-Cad and SN-Cad demonstrate a promoting effect on cell migration [47][48][49][50][51][52].…”

Ceramide AD™ Restores Skin Integrity and Function following Exposure to House Dust Mite

“…This was associated with increased in situ MMP-9 activity, reduced cutaneous expression of adherent protein Ecadherin, increased soluble E-cadherin in culture supernatant and significantly increased number of supra-basal melanocytes in the skin. This effect was dose-dependent and driven by HDM-containing cysteine protease Der p1 and MMP-9 [18].…”

“…Moreover, in addition to allergenic properties, there is evidence to suggest that the potent protease activity of mites can disrupt the skin epithelial barrier, promoting trans-epidermal water loss and facilitating the penetration of allergens directly into the skin [17]. We have recently shown that in human skin, HDM increased keratinocyte production of vitiligo-associated cytokines and chemokines [18]. This was associated with increased in situ MMP-9 activity, reduced cutaneous expression of adherent protein Ecadherin, increased soluble E-cadherin in culture supernatant and significantly increased number of supra-basal melanocytes in the skin.…”

The Effect of House Dust Sensitization on Skin Sebum and Moisture in Children with Allergic Respiratory Diseases

“…Furthermore, evidence suggests that house dust mites might contribute to the pathogenesis of intestinal destruction by compromising tight junctions between group 1 major allergens with cysteine protease activity and epithelial cells [ 19 ]. Apart from their significant impact on respiratory and gastrointestinal ailments, mites are recognized culprits in the development of atopic dermatitis, acne, and rosacea in human skin [ 20 , 21 ].…”