ArticleJournal of autoimmunity2019
Plcγ2/Tmem178 dependent pathway in myeloid cells modulates the pathogenesis of cytokine storm syndrome.
Article in Journal of autoimmunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The role of biomarkers in diagnosis of COVID-19 - A systematic review.Life sciences · 2020Pooled it
- Inflammation awakens dormant cancer cells by modulating the epithelial-mesenchymal phenotypic state.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Frontiers and hotspots evolution in cytokine storm: A bibliometric analysis from 2004 to 2022.Heliyon · 2024Article
- IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling.Gut · 2024Article
- Monocytic Phagocytes in the Immunopathogenesis of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Delayed macrophage targeting by clodronate liposomes worsens the progression of cytokine storm syndrome.Frontiers in immunology · 2024Article
- Tmem178 Negatively Regulates IL-1β Production Through Inhibition of the NLRP3 Inflammasome.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Murine Models of Secondary Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- The Multifaceted Immunology of Cytokine Storm Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- MicroRNAs and cytokines as potential predictive biomarkers for COVID-19 disease progression.Scientific reports · 2023Article
- Liposome encapsulated clodronate mediated elimination of pathogenic macrophages and microglia: A promising pharmacological regime to defuse cytokine storm in COVID-19.Medicine in drug discovery · 2022Review
- The roles of transmembrane family proteins in the regulation of store-operated CaCellular and molecular life sciences : CMLS · 2022Review
- Mechanisms of Immunothrombosis by SARS-CoV-2.Biomolecules · 2021Review
- The most important biomarker associated with coagulation and inflammation among COVID-19 patients.Molecular and cellular biochemistry · 2021Review
- Inflammation Unrestrained by SIRPα Induces Secondary Hemophagocytic Lymphohistiocytosis Independent of IFN-γ.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Intensive care management of patients with COVID-19.Journal of anaesthesiology, clinical pharmacology · 2020Review
- Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?Journal of autoimmunity · 2020Review
- Diacylglycerol Kinase ζ Regulates Macrophage Responses in Juvenile Arthritis and Cytokine Storm Syndrome Mouse Models.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Current Options in the Treatment of COVID-19: A Review.Risk management and healthcare policy · 2020Review
- The Role of T Cells and Macrophages in Asthma Pathogenesis: A New Perspective on Mutual Crosstalk.Mediators of inflammation · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cytokine storm syndrome (CSS) is a life-threatening condition characterized by excessive activation of T cells and uncontrolled inflammation, mostly described in patients with familial hemophagocytic lymphohistiocytosis and certain systemic auto-inflammatory diseases, such as systemic juvenile idiopathic arthritis (sJIA). Defects in T cell cytotoxicity as a mechanism for uncontrolled inflammation following viral infections fail to represent the whole spectrum of CSS. Evidence implicates dysregulated innate immune responses, especially activation of monocytes and macrophages, in patients with CSS. However, the direct contribution of monocytes/macrophages to CSS development and the signaling pathways involved in their activation have not been formally investigated. We find that depletion of monocytes/macrophages during early stages of CSS development, by clodronate-liposomes or neutralizing anti-CSF1 antibody, reduces mortality and inflammatory cytokine levels in two CSS mouse models, one dependent on T cells and the second induced by repeated TLR9 stimulation. We further demonstrate that activation of Plcγ2 in myeloid cells controls CSS development by driving macrophage pro-inflammatory responses. Intriguingly, the Plcγ2 downstream effector Tmem178, a negative modulator of calcium levels, acts in a negative feedback loop to restrain inflammatory cytokine production. Genetic deletion of Tmem178 leads to pro-inflammatory macrophage polarization in vitro and more severe CSS in vivo. Importantly, Tmem178 levels are reduced in macrophages from mice with CSS and after exposure to plasma from sJIA patients with active disease. Our data identify a novel Plcγ2/Tmem178 axis as a modulator of inflammatory cytokine production by monocytes/macrophages. We also find that loss of Tmem178 accentuates the pro-inflammatory responses in CSS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.