ArticleFrontiers in immunology2021
The Macrophage Reprogramming Ability of Antifolates Reveals Soluble CD14 as a Potential Biomarker for Methotrexate Response in Rheumatoid Arthritis.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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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.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Monocytes from inflammatory arthritis patients accumulate methotrexate and their transcriptome predicts methotrexate clinical response.Cellular and molecular life sciences : CMLS · 2026Article
- The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis.European journal of rheumatology · 2025Article
- Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases.Nature reviews. Rheumatology · 2025Review
- Article
- Targeted proteomics in extracellular vesicles identifies biomarkers predictive for therapeutic response in sarcoidosis.ERJ open research · 2025Article
- A review of gut failure as a cause and consequence of critical illness.Critical care (London, England) · 2025Review
- Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease.Cell reports · 2024Article
- Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis.Respiratory research · 2024Article
- Enhanced T-cell activation and chemokine-associated function in CD14-positive cells from venous sinus blood in sub-acute cerebral venous sinus thrombosis.Frontiers in cell and developmental biology · 2024Article
- Combination of Methotrexate and Resveratrol Reduces Pro-Inflammatory Chemokines in Human THP-1 Cells.Journal of inflammation research · 2024Article
- Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.Frontiers in immunology · 2024Article
- Innate immune memory in inflammatory arthritis.Nature reviews. Rheumatology · 2023Review
- Role of CD14 in human disease.Immunology · 2023Review
- Methotrexate Provokes Disparate Folate Metabolism Gene Expression and Alternative Splicing in Ex Vivo Monocytes and GM-CSF- and M-CSF-Polarized Macrophages.International journal of molecular sciences · 2023Article
- Predictors of improvement in disease activity in first hospitalized patients with systemic lupus erythematosus: a multicenter retrospective study of a Chinese cohort.Clinical rheumatology · 2022Article
- Folate Receptor Beta for Macrophage Imaging in Rheumatoid Arthritis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The identification of "trained immunity/tolerance" in myeloid cells has changed our perception of the performance of monocytes and macrophages during inflammatory and immune responses. Pemetrexed (PMX) and methotrexate (MTX) are blockers of the one-carbon metabolism (OCM) and commonly used therapeutic agents in cancer and rheumatoid arthritis (RA). We have previously showed that MTX promotes trained immunity in human macrophages. In the present manuscript, we have assessed the anti-inflammatory effects of PMX and MTX and found that OCM blockers alter the functional and gene expression profile of human macrophages and that OCM blockade reprograms macrophages towards a state of lipopolysaccharide (LPS) tolerance at the signaling and functional levels. Moreover, OCM blockade reduced macrophage LPS responsiveness by impairing the expression of membrane-bound and soluble CD14 (sCD14). The therapeutic relevance of these results was later confirmed in early RA patients, as MTX-responder RA patients exhibit lower sCD14 serum levels, with baseline sCD14 levels predicting MTX response. As a whole, our results demonstrate that OCM is a metabolic circuit that critically mediates the acquisition of innate immune tolerance and positions sCD14 as a valuable tool to predict MTX response in RA patients.
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