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| Item Type: | Dataset |
|---|---|
| Title: | IL-36 signaling as a drug target in Crohn's disease patients with IL36RN mutations |
| Creators Name: | Hecker, Julia, Plattner, Christina, Cancino, Camila A., Löscher, Britt-Sabina, Saurenbach, Judith, Letizia, Marilena, Rieder, Dietmar, Friese, Inka, Koop, Kristina, Neufert, Clemens, Dunkel, Désirée, Al Khatim, Zainab, Schaafs, Lars-Arne, Schuetz, Anja, Becker, Christoph, Atreya, Raja, Trajanoski, Zlatko, Franke, Andre, Sonnenberg, Elena, Ahmed N., Hegazy, Siegmund, Britta and Weidinger, Carl |
| Abstract: | The IL-36 signaling pathway has recently been identified as a key regulator of intestinal homeostasis and inflammation. However, the role of mutations in the IL-36R signaling pathway in the pathogenesis of inflammatory bowel disease remains unclear. We here identified four Crohn's disease patients with heterozygous missense mutations in the IL-36 receptor antagonist (IL36RN, IL-36RA). Experimental overexpression and functional assays demonstrated that two identified mutations resulted in reduced expression of IL-36RA. In-depth immune profiling of one IL36RN-mutated patient revealed an increased response of PBMCs to IL-36 stimulation and elevated serum levels of IL-36-regulated cytokines. Administration of the IL-36R-blocking antibody spesolimab to this patient resulted in a reduction of intestinal inflammation and alterations in immune cell composition and function. Our findings indicate that pathogenic IL36RN mutations may contribute to the pathogenesis of Crohn's disease in a subset of patients and that inhibiting IL-36 signaling could offer a personalized therapeutic approach for these patients. |
| Source: | Sourcedata |
| Publisher: | EMBO |
| Date: | 13 May 2025 |
| External Fulltext: | View full text on external repository or document server |
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