ArticleThe Journal of clinical investigation2022
Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.International journal of molecular sciences · 2026Article
- Review
- Elucidating the Causal Relationships Between B Cells, Dendritic Cells, and Multiple Sclerosis Pathogenesis.Brain and behavior · 2026Article
- PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.Nature reviews. Rheumatology · 2026Review
- TIGITFrontiers in immunology · 2026Review
- Next-generation immunotherapies for head and neck squamous cell carcinoma: targeting novel immune checkpoints.Annals of medicine · 2025Review
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- αTIGIT-IL2 achieves tumor regression by promoting tumor-infiltrating regulatory T cell fragility in mouse models.Nature communications · 2025Article
- TIGIT deficiency promotes autoreactive CD4Nature communications · 2025Article
- Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence.Aging cell · 2025Article
- Effects of Anti-CD20 Antibody Therapy on Immune Cell Dynamics in Relapsing-Remitting Multiple Sclerosis.Cells · 2025Article
- YiQiWenShen formula ameliorates myasthenia gravis through T follicular helper cells/T follicular regulatory cells immune rebalancing.American journal of translational research · 2025Article
- Review
- T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension.Respiratory research · 2024Article
- Unraveling disulfidptosis for prognostic modeling and personalized treatment strategies in lung adenocarcinoma.Future science OA · 2024Article
- Review
- The differentiation courses of the Tfh cells: a new perspective on autoimmune disease pathogenesis and treatment.Bioscience reports · 2024Review
- Human regulatory memory B cells defined by expression of TIM-1 and TIGIT are dysfunctional in multiple sclerosis.Frontiers in immunology · 2024Article
- TIGIT: an immune checkpoint beyond T cells in chronic lymphocytic leukemia.Haematologica · 2023Article
- Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
B cell depletion in patients with relapsing-remitting multiple sclerosis (RRMS) markedly prevents new MRI-detected lesions and disease activity, suggesting the hypothesis that altered B cell function leads to the activation of T cells driving disease pathogenesis. Here, we performed comprehensive analyses of CD40 ligand- (CD40L-) and IL-21-stimulated memory B cells from patients with MS and healthy age-matched controls, modeling the help of follicular helper T cells (Tfh cells), and found a differential gene expression signature in multiple B cell pathways. Most striking was the impaired TIGIT expression on MS-derived B cells mediated by dysregulation of the transcription factor TCF4. Activated circulating Tfh cells (cTfh cells) expressed CD155, the ligand of TIGIT, and TIGIT on B cells revealed their capacity to suppress the proliferation of IL-17-producing cTfh cells via the TIGIT/CD155 axis. Finally, CCR6+ cTfh cells were significantly increased in patients with MS, and their frequency was inversely correlated with that of TIGIT+ B cells. Together, these data suggest that the dysregulation of negative feedback loops between TIGIT+ memory B cells and cTfh cells in MS drives the activated immune system in this disease.
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What Socratic 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 Socratic graph.