1. Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease
- Author
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Patrick, Garrett J, Liu, Haiyun, Alphonse, Martin P, Dikeman, Dustin A, Youn, Christine, Otterson, Jack C, Wang, Yu, Ravipati, Advaitaa, Mazhar, Momina, Denny, George, Ortines, Roger V, Zhang, Emily, Miller, Robert J, Dillen, Carly A, Liu, Qi, Nolan, Sabrina J, Nguyen, Kristine, Marcello, LeeAnn, C., Danh, Wier, Eric M, Zhang, Yan, Caviness, Gary, Klimowicz, Alexander C, Mierz, Diane V, Fine, Jay S, Sun, Guangping, Goldbach-Mansky, Raphaela, Marusina, Alina I, Merleev, Alexander A, Maverakis, Emanual, Garza, Luis A, Milner, Joshua D, Gao, Peisong, Ramanujam, Meera, Raymond, Ernest L, Archer, Nathan K, and Miller, Lloyd S
- Subjects
Eczema / Atopic Dermatitis ,Infectious Diseases ,Food Allergies ,Lung ,Emerging Infectious Diseases ,Aetiology ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Skin ,Animals ,Cell Differentiation ,Dermatitis ,Atopic ,Humans ,Immunoglobulin Class Switching ,Immunoglobulin E ,Interleukin-1 ,Interleukin-4 ,Keratinocytes ,Mice ,Mice ,Knockout ,Plasma Cells ,Staphylococcus aureus ,Allergy ,Cytokines ,Immunology ,Inflammation ,Medical and Health Sciences - Abstract
IgE induced by type 2 immune responses in atopic dermatitis is implicated in the progression of atopic dermatitis to other allergic diseases, including food allergies, allergic rhinitis, and asthma. However, the keratinocyte-derived signals that promote IgE and ensuing allergic diseases remain unclear. Herein, in a mouse model of atopic dermatitis-like skin inflammation induced by epicutaneous Staphylococcus aureus exposure, keratinocyte release of IL‑36α along with IL-4 triggered B cell IgE class-switching, plasma cell differentiation, and increased serum IgE levels-all of which were abrogated in IL-36R-deficient mice or anti-IL‑36R-blocking antibody-treated mice. Moreover, skin allergen sensitization during S. aureus epicutaneous exposure-induced IL-36 responses was required for the development of allergen-specific lung inflammation. In translating these findings, elevated IL‑36 cytokines in human atopic dermatitis skin and in IL‑36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL‑36 responses represent a key mechanism and potential therapeutic target against allergic diseases.
- Published
- 2021