Epicutaneous Staphylococcus aureus induces IL-36 to enhance IgE production and ensuing allergic disease

Garrett J. Patrick, Haiyun Liu, Martin P. Alphonse, Dustin A. Dikeman, Christine Youn, Jack C. Otterson, Yu Wang, Advaitaa Ravipati, Momina Mazhar, George Denny, Roger V. Ortines, Emily Zhang, Robert J. Miller, Carly A. Dillen, Qi Liu, Sabrina J. Nolan, Kristine Nguyen, Lee Ann Marcello, Danh C. Do, Eric M. WierYan Zhang, Gary Caviness, Alexander C. Klimowicz, Diane V. Mierz, Jay S. Fine, Guangping Sun, Raphaela Goldbach-Mansky, Alina I. Marusina, Alexander A. Merleev, Emanual Maverakis, Luis A. Garza, Joshua D. Milner, Peisong Gao, Meera Ramanujam, Ernest L. Raymond, Nathan K. Archer, Lloyd S. Miller

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere143334
JournalJournal of Clinical Investigation
Volume131
Issue number5
DOIs
StatePublished - Mar 1 2021

ASJC Scopus subject areas

  • Medicine(all)

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