Acidification of stratum corneum prevents the progression from atopic dermatitis to respiratory allergy

Abstract

The presence of congenitally impaired skin barrier followed by atopic dermatitis (AD) is an initial step in the atopic march. The maintenance of acidic pH in the stratum corneum (SC) has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. To determine whether an AD murine model, flaky tail mice, with inherited filaggrin deficiency could develop airway inflammation by repeated topical application followed by nasal inhalation of house dust mite (HDM) antigen (defined as a novel "atopic march animal model"), and whether maintenance of an acidic SC environment by continuous application of acidic cream could interrupt the following atopic march. During the course of HDM treatment, acidic cream (pH2.8) or neutral cream (pH7.4) was applied to flaky tail mice twice daily. Repeated applications and inhalations of HDM to flaky tail mice induced AD skin lesions followed by respiratory allergies. Maintenance of SC acidity inhibited the occurrence of respiratory allergic inflammation as well as AD-like skin lesions. Collectively, a novel atopic march model could be developed by repeated epicutaneous and nasal applications of HDM to flaky tail mice, and that the acidification of SC could prevent the atopic march from AD to respiratory allergy.

Chitinase 3‐like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

“…BRP‐39 −/− mice were generated on a C57BL/6 background and maintained as previously described . Flg ft mice, which carry double‐homozygous Flg and matted (ma) gene mutations, with a BALB/c background were kindly provided by Kenji Kabashima (Kyoto University Graduate School of Medicine, Kyoto, Japan), and we backcrossed these with C57BL/6 mice over seven generations. For the OVA‐induced AD model, Flg ft mice were backcrossed with BRP‐39 −/− mice.…”

pH in nature, humans and skin

“…pH 4) and containing a functioning buffer system were introduced to counteract an increased pH. Treatment with an acidic compared with a neutral cream inhibited the occurrence of atopic dermatitis‐like skin lesions and respiratory allergy in filaggrin‐deficient murine atopic dermatitis models . An emollient with a pH of 4.8 altered skin barrier and microbes in infants at risk for developing atopic dermatitis .…”

“…Treatment with an acidic compared with a neutral cream inhibited the occurrence of atopic dermatitislike skin lesions and respiratory allergy in filaggrin-deficient murine atopic dermatitis models. [102][103][104] An emollient with a pH of 4.8 altered skin barrier and microbes in infants at risk for developing atopic dermatitis. 105 Skin care products adjusted to pH 4 have been used successfully in acne skin.…”

Role of Resveratrol in Regulating Cutaneous Functions

“…Importantly, recent studies showed that the epidermal dysfunction-induced elevations in cutaneous cytokines lead to increased levels of proinflammatory cytokines not only in the skin, but also in circulation, supporting not only a pathogenic role for epidermal function in cutaneous and extracutaneous inflammation, but also suggesting a link between cutaneous function and inflammation-associated systemic disorders [17,18]. In addition to epidermal permeability barrier homeostasis, other epidermal functions, such as pH and stratum corneum hydration, also regulate cutaneous functions [19][20][21][22]. Accordingly, improvements in epidermal function could benefit multiple cutaneous and extracutaneous functions [17,[23][24][25].…”