Academic Journal
Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients
| العنوان: | Profound inhibition of CD73-dependent formation of anti-inflammatory adenosine in B cells of SLE patients |
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| المؤلفون: | Julia Hesse, Magdalena Siekierka-Harreis, Bodo Steckel, Christina Alter, Merle Schallehn, Nadine Honke, Marie-Laure Schnieringer, Madita Wippich, Rebekka Braband, Matthias Schneider, Harald Surowy, Dagmar Wieczorek, Jürgen Schrader, Georg Pongratz |
| المصدر: | EBioMedicine, Vol 73, Iss , Pp 103616- (2021) |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Medicine (General) |
| مصطلحات موضوعية: | Purines, Metabolism, Autoimmune disease, CD38, CD39, Medicine, Medicine (General), R5-920 |
| الوصف: | Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that leads to a breakdown of tolerance to self-antigens resulting in inflammation and organ damage. The anti-inflammatory activity of CD73-derived adenosine is well documented, however, its role in SLE pathogenesis is unknown. Methods: Human peripheral blood immune cells were obtained from adult SLE patients (SLE) and healthy controls (HC). Expression and activity of purinergic ectoenzymes were assessed by qRT-PCR, flow cytometry and HPLC. Genes encoding purinergic ectoenzymes in SLE patients were analysed with targeted DNA sequencing. Findings: Among circulating immune cells (both in HC and SLE), CD73 was most highly expressed on B cells, which was mirrored by high enzymatic activity only in HC. CD73 protein molecular weight was unchanged in SLE, however, the enzymatic activity of CD73 on SLE B cells was almost fully abolished. Accordingly, AMP accumulated in cultured SLE B cells. A similar discrepancy between protein expression and enzymatic activity was observed for NAD-degrading CD38 on SLE B cells. No differences were found in the rate of extracellular ATP degradation and expression of CD39, CD203a/c, and CD157. DNA sequencing identified no coding variants in CD73 in SLE patients. Interpretation: We describe a new pathomechanism for SLE, by which inactivation of CD73 on B cells produces less anti-inflammatory adenosine, resulting in immune cell activation. CD73 inactivation was not due to genetic variation but may be related to posttranslational modification. Funding: The German Research Council, Medical Faculty of the Heinrich-Heine-University Duesseldorf, Hiller Research Foundation, and Cardiovascular Research Institute Duesseldorf. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2352-3964 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352396421004096; https://doaj.org/toc/2352-3964 |
| DOI: | 10.1016/j.ebiom.2021.103616 |
| URL الوصول: | https://doaj.org/article/3a3c067855944da7a11f780ad0c8a810 |
| رقم الانضمام: | edsdoj.3a3c067855944da7a11f780ad0c8a810 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2021.103616 |