دورية أكاديمية
ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome
العنوان: | ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome |
---|---|
المؤلفون: | Lola Rodríguez‐Ruiz, Juan M Lozano‐Gil, Elena Naranjo‐Sánchez, Elena Martínez‐Balsalobre, Alicia Martínez‐López, Christophe Lachaud, Miguel Blanquer, Toan K Phung, Diana García‐Moreno, María L Cayuela, Sylwia D Tyrkalska, Ana B Pérez‐Oliva, Victoriano Mulero |
المصدر: | EMBO Molecular Medicine, Vol 15, Iss 10, Pp n/a-n/a (2023) |
بيانات النشر: | Springer Nature, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Medicine (General) LCC:Genetics |
مصطلحات موضوعية: | anemia, HSPCs, inflammation, neutrophilia, zebrafish, Medicine (General), R5-920, Genetics, QH426-470 |
الوصف: | Abstract Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA‐approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1757-4684 1757-4676 20231814 |
العلاقة: | https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test |
DOI: | 10.15252/emmm.202318142 |
الوصول الحر: | https://doaj.org/article/b205befa4d104117853060fc54fa807bTest |
رقم الانضمام: | edsdoj.b205befa4d104117853060fc54fa807b |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 17574684 17574676 20231814 |
---|---|
DOI: | 10.15252/emmm.202318142 |