Topical application of celastrol alleviates atopic dermatitis symptoms mediated through the regulation of thymic stromal lymphopoietin and group 2 innate lymphoid cells

ABSTRACT

Atopic dermatitis is a chronic inflammatory skin disease, of which incidence is closely related to exposure to environmental pollutants and allergens. Thymic stromal lymphopoietin (TSLP) plays an important role in the early stages of atopic dermatitis development by inducing Th2 immune responses. In addition, TSLP regulates activation of group 2 innate lymphoid cells (ILC2), promoting the pathogenesis of atopic dermatitis. The aim of this study was to investigate whether celastrol alleviated atopic dermatitis symptoms by regulating TSLP expression and ILC2 stimulation. Celastrol suppressed TSLP production in mouse keratinocyte cells by inhibiting NF-ĸB activation. Topical application of celastrol significantly improved atopic dermatitis symptoms induced by house dust mite (HDM) in NC/Nga mice as determined by dermatitis score and histological assessment. Celastrol decreased the levels of TSLP in atopic dermatitis skin lesions of HDM-stimulated NC/Nga mice. Celastrol reduced levels of Th2 cytokines including IL-4, IL-5, and IL-13 in atopic dermatitis skin lesions of NC/Nga mice. Further, celastrol significantly reduced ILC2 population in atopic dermatitis skin lesions of NC/Nga mice. These results indicate that topical application of celastrol improved atopic dermatitis symptoms by lowering TSLP levels and concomitant immune responses. Data demonstrated that reduced TSLP levels and associated lower number of ILC2 cells alleviate atopic dermatitis symptoms induced by house dust mite.

KEYWORDS:

• Skin
• inflammation
• immunity
• environmental pollutants

Acknowledgments

This study was supported by the Research Fund, 2021 of The Catholic University of Korea, and grants from the National Research Foundation of Korea (NRF-2019R1A2C2085739 and NRF-2020R1A4A2002894) funded by the Korean government (Ministry of Science, ICT and Future Planning).

Disclosure statement

The authors declare that they have no competing interests.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.