Inflammasomes—New Contributors to Blood Diseases
Abstract
:1. Introduction
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- Pattern-recognition receptors (PRRs)—molecules predominantly belonging to the NOD-like receptor (NLR) family, that detect a wide array of activators. Moreover, absent-in-melanoma-2-like (AIM2-like) receptors and pyrin are also reported as PRRs forming the inflammasomes [4], serving as exclusive exogenous DNA and toxin detectors, respectively [1,5]. The PRR component is essential for the inflammasome to initiate its function.
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- Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)—an adaptor protein composed of a pyrin domain (PYD), enabling association with the PRR component, and a caspase activation and recruitment domain (CARD), which facilitates the binding of pro-caspase-1 to the PRR–ASC complex. The adaptor protein is absent once PRR contains the CARD domain [4].
- −
- Pro-caspase-1—an inactive form of caspase-1, a protease that cleaves the precursors of IL-1β and IL-18 cytokines and other proteins, for instance, gasdermin D [4]. It is activated upon inflammasome assembly, which is elicited by detecting a specific activating signal by PRR and subsequent association of the discussed components [4]. As a result, pro-caspase-1 undergoes autocleavage to form active caspase-1 [6].
Inflammasome Priming and Activation Mechanisms
2. Myelodysplastic Neoplasms
3. Lymphomas
4. Multiple Myeloma
5. Leukemias
5.1. Acute Myeloid Leukemia
5.2. Chronic Myeloid Leukemia
5.3. Acute Lymphoblastic Leukemia
5.4. Chronic Lymphocytic Leukemia
6. Hemophagocytic Lymphohistiocytosis
7. Graft-Versus-Host Disease
8. Sickle Cell Anemia
9. Inflammasomes and Immunotherapies
10. Discussion
11. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Disease | Inflammasome Type | Expression Status | Key Cytokines | Role in Pathogenesis | Related Signaling Pathways | Ref. |
---|---|---|---|---|---|---|
Myelodysplastic Neoplasms (MDS) | NLRP3 | Upregulated | IL-1β and IL-18 | pyroptosis of MDS cells triggers an inflammatory response and promotes the proliferation of neoplastic cells | TLR4/MyD88/IRAK1, IRAK4/TRAF6/NF-κB WNT/β -catenin | [8,12,16,17,18,19] |
Diffuse Large B-Cell Lymphoma (DLBCL) | NLRP3 | Upregulated | IL-18 | NLRP3 inflammasome promotes cell proliferation and apoptosis inhibition and reduces the therapeutic effect of dexamethasone | NLRP3/IL-18/IFN-Y/JAK-STAT/IRF/PD-L1 | [23,25] |
EBV-positive Burkitt Lymphoma | NLRP3 | Downregulated | IL-1β | downregulated NLRP3 inflammasome cannot prevent latent EBV infection NLRP11 molecule represses NLRP3 expression by inhibiting the NF-κB pathway | TLR4/MyD88/TRAF6/NF-κB pathway | [26,27,28] |
Marginal Zone Lymphoma | NLRP3 | Upregulated | IL-1β and IL-18 | lymphomagenesis, NLRP3 inflammasome promotes formation of GC-like structures | P2 × 7R-NLRP3 axis | [30,31] |
Adult T-cell Lymphoma (ATL) | NLRP3 | Upregulated artificially by HBI-8000 drug | IL-1β | NLRP3 inflammasome prevents latent HTLV-1 infection | not mentioned in the reference | [33] |
Multiple Myeloma (MM) | NLRP1, NLRP3 | Upregulated | IL-18 | NLRP1-dependent activation of MDSCs enables MM cells to evade immune control β2 microglobulin accumulation in myeloma-associated macrophages causes NLRP3-dependent inflammatory response promoting myeloma cell proliferation | unknown | [35,36] |
Acute Myeloid Leukemia (AML) | NLRP3 | Upregulated | IL-1β and IL-18 | NLRP3 inflammasome overexpression in AML cells promotes proliferation and survival NLRP3 inflammasome activation in bone marrow dendritic cells induces Th1 response promoting apoptosis and inhibiting proliferation of AML cells | HMGB1/TLR4, TLR2, RAGE/MyD88/NF-κB IFN-γ/STAT1 pathway in Th1 lymphocytes | [40,42,43] |
Chronic Myeloid Leukemia (CML) | NLRP1 | Upregulated | IL-1β | NLRP1 inflammasome suppresses apoptosis and promotes proliferation of CML cells and imatinib resistance | IRE1α/CREB/NLRP1 pathway associated with Endoplasmic Reticulum Stress | [44] |
Acute Lymphoblastic Leukemia (ALL) | NLRP3 | Upregulated | - | caspase-1 cleaves glucocorticoid receptors in their transactivation domain, contributing to glucocorticoid resistance | hypomethylation of NLRP3 and CASP1 (caspase-1 gene) promoters | [46] |
Chronic Lymphocytic Leukemia (CLL) | NLRP3 | Downregulated | IL-1β | NLRP3 inflammasome downregulation promotes proliferation of CLL cells | P2 × 7R/NLRP3 axis | [49] |
Hemophagocytic Lymphohistiocytosis (HLH) | NLRC4 | Upregulated | IL-18 | T cell exhaustion death causes a release of alarmins activating macrophages, which subsequently undergo pyroptosis contributing to inflammation in the positive feedback loop | unspecified TLR and IFN-γ signaling pathways | [51,52,54,75] |
Graft-versus-Host Disease (GvHD) | NLRP3 | Upregulated | IL-1β and IL-18 | NLRP3 inflammasome activation induces overexpression of costimulatory molecules on APCs, promoting alloreactive T cells response NLRP3 inflammasome activation in MDSCs impedes their anti-inflammatory function by reducing arginase production conditioning-induced mucosal damage promotes the inflammasome-dependent response | TLR4/MyD88/TRIF/NF-κB | [58,59,60,61] |
Sickle Cell Anemia (SCA) | NLRP3 | Upregulated | IL-1β and IL-18 | hemolysis-related alarmins activate NLRP3 inflammasomes in platelets leading to aggregation of platelets | HMGB1/TLR4/MyD88/IRAK4/NF-κB BTK kinase signaling | [66,67,68,69,70] |
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Tomasik, J.; Basak, G.W. Inflammasomes—New Contributors to Blood Diseases. Int. J. Mol. Sci. 2022, 23, 8129. https://doi.org/10.3390/ijms23158129
Tomasik J, Basak GW. Inflammasomes—New Contributors to Blood Diseases. International Journal of Molecular Sciences. 2022; 23(15):8129. https://doi.org/10.3390/ijms23158129
Chicago/Turabian StyleTomasik, Jaromir, and Grzegorz Władysław Basak. 2022. "Inflammasomes—New Contributors to Blood Diseases" International Journal of Molecular Sciences 23, no. 15: 8129. https://doi.org/10.3390/ijms23158129