| First Author | Patrick GJ | Year | 2021 |
| Journal | J Clin Invest | Volume | 131 |
| Issue | 5 | PubMed ID | 33645549 |
| Mgi Jnum | J:332779 | Mgi Id | MGI:7428521 |
| Doi | 10.1172/JCI143334 | Citation | Patrick GJ, et al. (2021) Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease. J Clin Invest 131(5) |
| abstractText | 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 IL36alpha 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-IL36R-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 IL36 cytokines in human atopic dermatitis skin and in IL36 receptor antagonist-deficiency patients coincided with increased serum IgE levels. Collectively, keratinocyte-initiated IL36 responses represent a key mechanism and potential therapeutic target against allergic diseases. |
