دورية أكاديمية
Cholesterol metabolism promotes B‐cell positioning during immune pathogenesis of chronic obstructive pulmonary disease
| العنوان: | Cholesterol metabolism promotes B‐cell positioning during immune pathogenesis of chronic obstructive pulmonary disease |
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| المؤلفون: | Jie Jia, Thomas M Conlon, Rim SJ Sarker, Demet Taşdemir, Natalia F Smirnova, Barkha Srivastava, Stijn E Verleden, Gizem Güneş, Xiao Wu, Cornelia Prehn, Jiaqi Gao, Katharina Heinzelmann, Jutta Lintelmann, Martin Irmler, Stefan Pfeiffer, Michael Schloter, Ralf Zimmermann, Martin Hrabé de Angelis, Johannes Beckers, Jerzy Adamski, Hasan Bayram, Oliver Eickelberg, Ali Önder Yildirim |
| المصدر: | EMBO Molecular Medicine, Vol 10, Iss 5, Pp n/a-n/a (2018) |
| بيانات النشر: | Springer Nature, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | B cell, chronic obstructive pulmonary disease, inducible bronchus‐associated lymphoid tissue, oxysterol, tertiary lymphoid organ, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract The development of chronic obstructive pulmonary disease (COPD) pathogenesis remains unclear, but emerging evidence supports a crucial role for inducible bronchus‐associated lymphoid tissue (iBALT) in disease progression. Mechanisms underlying iBALT generation, particularly during chronic CS exposure, remain to be defined. Oxysterol metabolism of cholesterol is crucial to immune cell localization in secondary lymphoid tissue. Here, we demonstrate that oxysterols also critically regulate iBALT generation and the immune pathogenesis of COPD. In both COPD patients and cigarette smoke (CS)‐exposed mice, we identified significantly upregulated CH25H and CYP7B1 expression in airway epithelial cells, regulating CS‐induced B‐cell migration and iBALT formation. Mice deficient in CH25H or the oxysterol receptor EBI2 exhibited decreased iBALT and subsequent CS‐induced emphysema. Further, inhibition of the oxysterol pathway using clotrimazole resolved iBALT formation and attenuated CS‐induced emphysema in vivo therapeutically. Collectively, our studies are the first to mechanistically interrogate oxysterol‐dependent iBALT formation in the pathogenesis of COPD, and identify a novel therapeutic target for the treatment of COPD and potentially other diseases driven by the generation of tertiary lymphoid organs. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| العلاقة: | https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test |
| DOI: | 10.15252/emmm.201708349 |
| الوصول الحر: | https://doaj.org/article/97fa922cf1de46cda5b806cfa389d804Test |
| رقم الانضمام: | edsdoj.97fa922cf1de46cda5b806cfa389d804 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.201708349 |