ArticleEMBO molecular medicine2023
ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- A New Gain-of-Function NLRP1 Variant Is Associated with Inflammasome Activation and Disease Severity in SLC25A38 Congenital Sideroblastic Anemia Case Report.Journal of personalized medicine · 2026Article
- Ninjurins regulate hematopoietic stem cell amplification through canonical WNT signaling independent of plasma membrane rupture.Nature communications · 2026Article
- Rutin Alleviates Oxidative Stress in Chicken Hepatocytes by Inhibiting Ribotoxic Stress Response.Animals : an open access journal from MDPI · 2026Article
- M2 Macrophage-Derived Exosomes Ameliorate BPD by Inhibiting Ferroptosis via Suppression of the ZAKα-p38 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- TKI-mediated inhibition of NLRP1 inflammasome restores erythropoiesis in DBA syndrome.EMBO molecular medicine · 2026Article
- Programmed cell death pathways coordinate neutrophil and macrophage clearance in zebrafish and are differentially exploited by Salmonella Typhimurium.Cell death & disease · 2025Article
- Reduced GATA1 levels are associated with ineffective erythropoiesis in sickle cell anemia.Haematologica · 2025Article
- Spironolactone inhibits the NLRP1 inflammasome and alleviates defective erythropoiesis in Diamond-Blackfan anemia.HemaSphere · 2025Article
- Inflammasomes: potential therapeutic targets in hematopoietic stem cell transplantation.Cell communication and signaling : CCS · 2024Review
- Article
- ZAKα/P38 kinase signaling pathway regulates hematopoiesis by activating the NLRP1 inflammasome.EMBO molecular medicine · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
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.
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