دورية أكاديمية
IL-1 Mediates Microbiome-Induced Inflamm-Ageing of Hematopoietic Stem Cells in Mice
| العنوان: | IL-1 Mediates Microbiome-Induced Inflamm-Ageing of Hematopoietic Stem Cells in Mice |
|---|---|
| المؤلفون: | Kovtonyuk, Larisa Vladimirovna, Caiado, Francisco, Garcia-Martin, Santiago, Manz, Eva-Maria, Helbling, Patrick Michael, Takizawa, Hitoshi, Boettcher, Steffen, Al-Shahrour, Fatima, Nombela-Arrieta, Cesar, Slack, Emma, Manz, Markus G |
| المصدر: | Kovtonyuk, Larisa Vladimirovna; Caiado, Francisco; Garcia-Martin, Santiago; Manz, Eva-Maria; Helbling, Patrick Michael; Takizawa, Hitoshi; Boettcher, Steffen; Al-Shahrour, Fatima; Nombela-Arrieta, Cesar; Slack, Emma; Manz, Markus G (2022). IL-1 Mediates Microbiome-Induced Inflamm-Ageing of Hematopoietic Stem Cells in Mice. Blood, 139(1):44-58. |
| بيانات النشر: | American Society of Hematology |
| سنة النشر: | 2022 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Clinic for Oncology and Hematology, 610 Medicine & health |
| الوصف: | Ageing is associated with impaired hematopoietic and immune function. This is caused in part by decreased hematopoietic stem cell (HSC) population fitness and an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. We here demonstrate that aged specific pathogen free (SPF) wild-type mice in contrast to young SPF mice produce more IL-1a/b in steady-state bone marrow (BM), with most of IL-1a/b being derived from myeloid BM cells. Further, blood of steady-state aged SPF wild-type mice contains higher levels of microbe associated molecular patterns (MAMPs), specifically TLR4 and TLR8 ligands. Also, BM myeloid cells from aged mice produce more IL-1b in vitro, and aged mice show higher and more durable IL-1a/b responses upon LPS stimulation in vivo. To test if HSC ageing is driven via IL-1a/b, we evaluated HSCs from IL-1 receptor 1 (IL-1R1) knock-out mice. Indeed, aged HSCs from IL-1R1 knock-out mice show significantly mitigated ageing-associated inflammatory signatures. Moreover, HSCs from aged IL-1R1KO and also from germ-free mice maintain unbiased lympho-myeloid hematopoietic differentiation upon transplantation, thus resembling this functionality of young HSCs. Importantly, in vivo antibiotic suppression of microbiota or pharmacologic blockade of IL-1 signaling in aged wild-type mice was similarly sufficient to reverse myeloid biased output of their HSC populations. Collectively, our data defines the microbiome-IL-1/IL-1R1 axis as a key, self-sustaining, but also therapeutically partially reversible driver of HSC inflamm-ageing. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0006-4971 |
| العلاقة: | https://www.zora.uzh.ch/id/eprint/207125/1/blood.2021011570.pdfTest; info:pmid/34525198; urn:issn:0006-4971 |
| DOI: | 10.5167/uzh-207125 |
| DOI: | 10.1182/blood.2021011570 |
| الإتاحة: | https://doi.org/10.5167/uzh-20712510.1182/blood.2021011570Test https://www.zora.uzh.ch/id/eprint/207125Test/ https://www.zora.uzh.ch/id/eprint/207125/1/blood.2021011570.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.A2040239 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00064971 |
|---|---|
| DOI: | 10.5167/uzh-207125 |