ArticleEuropean journal of immunology2021
Tofacitinib therapy intercepts macrophage metabolic reprogramming instigated by SARS-CoV-2 Spike protein.
Article in European journal of immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Fibroblast-like Synoviocytes as Therapeutic Targets in Rheumatoid Arthritis: Current Evidence on DMARD-Mediated Modulation.Biomedicines · 2026Review
- JAK/STAT inhibition reprograms T cell activation and metabolism in inflammatory arthritis patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Tofacitinib repairs inflammation and mitochondrial dysregulation in GM-CSF-reprogrammed RA macrophages.Cellular & molecular immunology · 2026Article
- New mesenchymal stem/stromal cell-based strategies for osteoarthritis treatment: targeting macrophage-mediated inflammation to restore joint homeostasis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Review
- Large-scale computational modelling of the M1 and M2 synovial macrophages in rheumatoid arthritis.NPJ systems biology and applications · 2024Article
- Antiviral response and immunopathogenesis of interleukin 27 in COVID-19.Archives of virology · 2023Article
- Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.United European gastroenterology journal · 2023Article
- Small molecules in the treatment of COVID-19.Signal transduction and targeted therapy · 2022Review
- Targeting fibroblast-like synoviocytes in rheumatoid arthritis.Current opinion in pharmacology · 2022Review
- Tofacitinib enhances IGF1 via inhibiting STAT6 transcriptionally activated-miR-425-5p to ameliorate inflammation in RA-FLS.Molecular and cellular biochemistry · 2022Article
- Roles of Interleukin-6-mediated immunometabolic reprogramming in COVID-19 and other viral infection-associated diseases.International immunopharmacology · 2022Review
- Inhibition of IRAK4 dysregulates SARS-CoV-2 spike protein-induced macrophage inflammatory and glycolytic reprogramming.Cellular and molecular life sciences : CMLS · 2022Article
- Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- IRAK4 inhibitor mitigates joint inflammation by rebalancing metabolism malfunction in RA macrophages and fibroblasts.Life sciences · 2021Article
- Metabolic regulation of RA macrophages is distinct from RA fibroblasts and blockade of glycolysis alleviates inflammatory phenotype in both cell types.Cellular and molecular life sciences : CMLS · 2021Article
- A narrative review on tofacitinib: The properties, function, and usefulness to treat coronavirus disease 2019.International journal of critical illness and injury scienceReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein was characterized to identify novel therapies. The impact of tofacitinib, IL-6R Ab, or TNFi therapy was determined on Spike protein or LPS/IFN-γ-induced signaling, inflammation, and metabolic reprogramming in MΦs and/or rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS). ACE2 frequency was markedly expanded in MΦs compared to T cells and RA FLS. Tofacitinib suppresses Spike protein potentiated STAT1 signaling, whereas this function was unchanged by TNFi. Tofacitinib impairs IL-6/IFN/LPS-induced STAT1 and STAT3 phosphorylation in RA MΦs and FLS. Interestingly, tofacitinib had a broader inhibitory effect on the monokines, glycolytic regulators, or oxidative metabolites compared to IL-6R Ab and TNFi in Spike-protein-activated MΦs. In contrast, all three therapies disrupted IFN-α and IFN-β secretion in response to Spike protein; nonetheless, the IFN-γ was only curtailed by tofacitinib or IL-6R Ab. While tofacitinib counteracted MΦ metabolic rewiring instigated by Spike protein, it was inconsequential on the glycolysis expansion mediated via HK2 and/or LDHA in the activated RA MΦ and FLS. Nevertheless, the potentiated inflammatory response and the diminished oxidative phosphorylation modulated by Spike protein and/or LPS/IFN-γ stimulation in MΦs or RA FLS were reversed by tofacitinib. In conclusion, tofacitinib suppresses MΦ inflammation and immunometabolism triggered by Spike protein and may provide a promising strategy for COVID-19 patients.
Indexed as
Identifiers
What OpenQuestion holds
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.