ArticleActa neuropathologica2022
BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy.
Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- B-cell centrality dictates therapeutic efficacy across autoimmune diseases: a systematic review.Frontiers in immunology · 2026Pooled it
- First-in-Human Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of BIIB091, an Oral BTK Inhibitor, in Healthy Adult Participants.Drug design, development and therapy · 2026Trial
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Immunometabolic reprogramming in multiple sclerosis: from pathogenic amplifier to therapeutic target in neuroinflammation and remyelination.Inflammopharmacology · 2026Review
- BRG1-mediated suppression of ferroptosis underlies BTK inhibitor resistance.Nature communications · 2026Article
- Review
- Review
- Role of Bruton's Tyrosine Kinase in mast cell driven urothelial barrier injury in an LL-37 induced model of interstitial cystitis.Scientific reports · 2026Article
- Leveraging Kinase Drugs for Neurosciences: Discovery of Selective, CNS-Penetrant Reversible Bruton's Tyrosine Kinase Inhibitors as Therapeutics for Neuroinflammation.Journal of medicinal chemistry · 2026Article
- [Characterization of Immune Reconstitution Patterns in B-cell Subsets Mediated by B-cell Targeted Therapies].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- T cell-mediated immunodysregulation in multiple sclerosis: from pathogenic subsets to therapeutic advances.Frontiers in immunology · 2026Review
- Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.Current neuropharmacology · 2026Review
- Multiple skin tumors in a patient treated with orelabrutinib for mantle-cell lymphoma: Case report.Medicine · 2025Article
- Beyond relapses: How BTK inhibitors are shaping the future of progressive MS treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- Bruton's Tyrosine Kinase: A Potential Novel Target for Neurological Disorders.Physiological research · 2025Review
- Review
- B cell immunometabolism in health and disease.Nature immunology · 2025Review
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Inhibition of Bruton's Tyrosine Kinase (BTKi) is now viewed as a promising next-generation B-cell-targeting therapy for autoimmune diseases including multiple sclerosis (MS). Surprisingly little is known; however, about how BTKi influences MS disease-implicated functions of B cells. Here, we demonstrate that in addition to its expected impact on B-cell activation, BTKi attenuates B-cell:T-cell interactions via a novel mechanism involving modulation of B-cell metabolic pathways which, in turn, mediates an anti-inflammatory modulation of the B cells. In vitro, BTKi, as well as direct inhibition of B-cell mitochondrial respiration (but not glycolysis), limit the B-cell capacity to serve as APC to T cells. The role of metabolism in the regulation of human B-cell responses is confirmed when examining B cells of rare patients with mitochondrial respiratory chain mutations. We further demonstrate that both BTKi and metabolic modulation ex vivo can abrogate the aberrant activation and costimulatory molecule expression of B cells of untreated MS patients. Finally, as proof-of-principle in a Phase 1 study of healthy volunteers, we confirm that in vivo BTKi treatment reduces circulating B-cell mitochondrial respiration, diminishes their activation-induced expression of costimulatory molecules, and mediates an anti-inflammatory shift in the B-cell responses which is associated with an attenuation of T-cell pro-inflammatory responses. These data collectively elucidate a novel non-depleting mechanism by which BTKi mediates its effects on disease-implicated B-cell responses and reveals that modulating B-cell metabolism may be a viable therapeutic approach to target pro-inflammatory B cells.
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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.