Inflammasomes: Potential Therapeutic Targets in Hematopoietic Stem Cell Transplantation

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2024 Dec 19

PMID 39695742

Authors

Jieya Luo

Yunxia Zhou

Mingyang Wang

Junan Zhang

Erlie Jiang

Affiliations

Soon will be listed here.

Abstract

The realm of hematopoietic stem cell transplantation (HSCT) has witnessed remarkable advancements in elevating the cure and survival rates for patients with both malignant and non-malignant hematologic diseases. Nevertheless, a considerable number of patients continue to face challenges, including transplant-related complications, infection, graft failure, and mortality. Inflammasomes, the multi-protein complexes of the innate immune system, respond to various danger signals by releasing inflammatory cytokines and even mediating cell death. While moderate activation of inflammasomes is essential for immune defense and homeostasis maintenance, excessive activation precipitates inflammatory damage. The intricate interplay between HSCT and inflammasomes arises from their pivotal roles in immune responses and inflammation. This review examines the molecular architecture and composition of various types of inflammasomes, highlighting their activation and effector mechanisms within the context of the HSCT process and its associated complications. Additionally, we summarize the therapeutic implications of targeting inflammasomes and related factors in HSCT.

References

Jiang X, Wu X, Xiao Y, Wang P, Zheng J, Wu X . The ectonucleotidases CD39 and CD73 on T cells: The new pillar of hematological malignancy. Front Immunol. 2023; 14:1110325. PMC: 9911447. DOI: 10.3389/fimmu.2023.1110325. View

Little M, Storb R . History of haematopoietic stem-cell transplantation. Nat Rev Cancer. 2002; 2(3):231-8. DOI: 10.1038/nrc748. View

Wu K, Yuan Y, Yu H, Dai X, Wang S, Sun Z . The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice. Blood. 2020; 136(4):501-515. PMC: 7378459. DOI: 10.1182/blood.2019003990. View

Yao Y, Chen S, Cao M, Fan X, Yang T, Huang Y . Antigen-specific CD8 T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin. Nat Commun. 2017; 8:15402. PMC: 5458103. DOI: 10.1038/ncomms15402. View

Di Virgilio F, Schmalzing G, Markwardt F . The Elusive P2X7 Macropore. Trends Cell Biol. 2018; 28(5):392-404. DOI: 10.1016/j.tcb.2018.01.005. View

Zhu Q, Man S, Karki R, Malireddi R, Kanneganti T . Detrimental Type I Interferon Signaling Dominates Protective AIM2 Inflammasome Responses during Francisella novicida Infection. Cell Rep. 2018; 22(12):3168-3174. PMC: 6204211. DOI: 10.1016/j.celrep.2018.02.096. View

Xu Z, Kombe Kombe A, Deng S, Zhang H, Wu S, Ruan J . NLRP inflammasomes in health and disease. Mol Biomed. 2024; 5(1):14. PMC: 11033252. DOI: 10.1186/s43556-024-00179-x. View

Wu B, Jiang C, Jin L, Azadan X, Lin J, Lin L . Serum cytokine profiles during engraftment syndrome and acute graft-versus-host disease in adult patients after hematopoietic stem cell transplantation. Cytokine. 2024; 178:156582. DOI: 10.1016/j.cyto.2024.156582. View

Huang Y, Liu L, Ma D, Liao Y, Lu Y, Huang H . Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP-1-derived macrophages. J Med Virol. 2017; 89(12):2188-2195. DOI: 10.1002/jmv.24846. View

10.

Roy S, Rizvi Z, Awasthi A . Metabolic Checkpoints in Differentiation of Helper T Cells in Tissue Inflammation. Front Immunol. 2019; 9:3036. PMC: 6340303. DOI: 10.3389/fimmu.2018.03036. View

11.

Antin J, Weisdorf D, Neuberg D, Nicklow R, Clouthier S, Lee S . Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood. 2002; 100(10):3479-82. DOI: 10.1182/blood-2002-03-0985. View

12.

Ratajczak M, Kucia M . Extracellular Adenosine Triphosphate (eATP) and Its Metabolite, Extracellular Adenosine (eAdo), as Opposing "Yin-Yang" Regulators of Nlrp3 Inflammasome in the Trafficking of Hematopoietic Stem/Progenitor Cells. Front Immunol. 2021; 11:603942. PMC: 7878390. DOI: 10.3389/fimmu.2020.603942. View

13.

Wu J, Zhang W, Ran Q, Xiang Y, Zhong J, Li S . The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis. Stem Cells Int. 2018; 2018:1540148. PMC: 5903338. DOI: 10.1155/2018/1540148. View

14.

Broz P, Pelegrin P, Shao F . The gasdermins, a protein family executing cell death and inflammation. Nat Rev Immunol. 2019; 20(3):143-157. DOI: 10.1038/s41577-019-0228-2. View

15.

Chiusolo P, Giammarco S, Fanali C, Bellesi S, Metafuni E, Sica S . Salivary proteomic analysis and acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(6):888-92. DOI: 10.1016/j.bbmt.2013.03.011. View

16.

Ratajczak M, Adamiak M, Abdelbaset-Ismail A, Bujko K, Thapa A, Chumak V . Intracellular complement (complosome) is expressed in hematopoietic stem/progenitor cells (HSPCs) and regulates cell trafficking, metabolism and proliferation in an intracrine Nlrp3 inflammasome-dependent manner. Leukemia. 2023; 37(6):1401-1405. PMC: 10244163. DOI: 10.1038/s41375-023-01894-0. View

17.

Zhao Y, Yang J, Shi J, Gong Y, Lu Q, Xu H . The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature. 2011; 477(7366):596-600. DOI: 10.1038/nature10510. View

18.

Prochnicki T, Latz E . Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control. Cell Metab. 2017; 26(1):71-93. DOI: 10.1016/j.cmet.2017.06.018. View

19.

Man S, Karki R, Kanneganti T . Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017; 277(1):61-75. PMC: 5416822. DOI: 10.1111/imr.12534. View

20.

Abdelbaset-Ismail A, Ciechanowicz A, Bujko K, Ratajczak J, Kucia M, Ratajczak M . The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation. Stem Cell Rev Rep. 2022; 19(1):92-103. PMC: 9823029. DOI: 10.1007/s12015-022-10481-2. View