ArticleThe Journal of clinical investigation2017
Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The trial behind it
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Who cites it
55 citing papers in PubMed, 81 citations in OpenAlex.
- Review
- NFAT5 dictates crosstalk between intestinal epithelial regenerative capacity and microbiota in murine colitis models.The Journal of clinical investigation · 2025Article
- Immune Aging in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Interaction of the endogenous antibody response with activating FcγRs enhance control of Mayaro virus through monocytes.PLoS pathogens · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- NFAT5 counters long-term IFN-1 responses in hematopoietic stem cells to preserve reconstitution potential.Blood advances · 2024Article
- Activating FcγRs on monocytes are necessary for optimal Mayaro virus clearance.bioRxiv : the preprint server for biology · 2024Article
- The acute phase reactant orosomucoid-2 directly promotes rheumatoid inflammation.Experimental & molecular medicine · 2024Article
- Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.The Journal of clinical investigation · 2024Article
- Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis.Cellular & molecular immunology · 2024Article
- GRK2 inhibits Flt-1Acta pharmaceutica Sinica. B · 2024Article
- Regulation of Microtubule Stability in Pulmonary Microvascular Endothelial Cells in Rats with Severe Acute Pancreatitis: Qingyi Decoction is a Potential CDK5 Inhibitor.Journal of inflammation research · 2024Article
- Investigating Chemokine-Matrix Networks in Breast Cancer: Tenascin-C Sets the Tone for CCL2.International journal of molecular sciences · 2023Article
- Astrocyte-Derived Exosomes Differentially Shape T Cells' Immune Response in MS Patients.International journal of molecular sciences · 2023Article
- The role of the osmosensitive transcription factor NFAT5 in corneal edema resorption after injury.Experimental & molecular medicine · 2023Article
- NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Hypoxia-inducible factor 1α enhances RANKL-induced osteoclast differentiation by upregulating the MAPK pathway.Annals of translational medicine · 2022Article
- Bone marrow mesenchymal stem cell-derived exosomal microRNA-381-3p alleviates vascular calcification in chronic kidney disease by targeting NFAT5.Cell death & disease · 2022Article
- Review
- Isoform-Selective NFAT Inhibitor: Potential Usefulness and Development.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective apoptotic death of activated macrophages has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining apoptotic resistance of RA macrophages are not fully understood. Here, global transcriptome profiling of RA macrophages revealed that the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) critically regulates diverse pathologic processes in synovial macrophages including the cell cycle, apoptosis, and proliferation. Transcriptomic analysis of NFAT5-deficient macrophages revealed the molecular networks defining cell survival and proliferation. Proinflammatory M1-polarizing stimuli and hypoxic conditions were responsible for enhanced NFAT5 expression in RA macrophages. An in vitro functional study demonstrated that NFAT5-deficient macrophages were more susceptible to apoptotic death. Specifically, CCL2 secretion in an NFAT5-dependent fashion bestowed apoptotic resistance to RA macrophages in vitro. Injection of recombinant CCL2 into one of the affected joints of Nfat5+/- mice increased joint destruction and macrophage infiltration, demonstrating the essential role of the NFAT5/CCL2 axis in arthritis progression in vivo. Moreover, after intra-articular injection, NFAT5-deficient macrophages were more susceptible to apoptosis and less efficient at promoting joint destruction than were NFAT5-sufficient macrophages. Thus, NFAT5 regulates macrophage survival by inducing CCL2 secretion. Our results provide evidence that NFAT5 expression in macrophages enhances chronic arthritis by conferring apoptotic resistance to activated macrophages.
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