Nlrp3 Inflammasome Signaling Regulates the Homing and Engraftment of Hematopoietic Stem Cells (HSPCs) by Enhancing Incorporation of CXCR4 Receptor into Membrane Lipid Rafts

• DOI: 10.1007/s12015-020-10005-w
• Publication Date: 2020-07-13T22:02:54Z
• Authors: Mateusz Adamiak; Ahmed Abdel-Latif; Kamila Bujko; Arjun Thapa; Krzysztof Anusz; Michał Tracz; Katarzyna Brzezni...; Janina Ratajczak; Magda Kucia; Mariusz Z. Ratajczak
• Keywords: Homing (biology); Lipid raft

Fast and efficient homing engraftment of hematopoietic stem progenitor cells (HSPCs) is crucial for positive clinical outcomes from transplantation. We found that this process depends on activation the Nlrp3 inflammasome, both in HSPCs to be transplanted recipient bone marrow (BM) microenvironment. For first time we provide evidence functional deficiency inflammasome or host microenvironment leads defective engraftment. At molecular level, their migration response major BM chemoattractant stromal-derived factor 1 (SDF-1) other supportive chemoattractants, including sphingosine-1-phosphate (S1P) extracellular adenosine triphosphate (eATP). report increases autocrine release eATP, which promotes incorporation CXCR4 receptor into membrane lipid rafts at leading surface migrating cells. On hand, a lack expression conditioned transplantation decrease SDF-1 danger-associated pattern molecules (DAMPs), are responsible complement cascade (ComC), turn facilitates HSPCs.