ArticleFrontiers in immunology2022
Tofacitinib Suppresses Natural Killer Cells
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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
22 citing papers in PubMed, 29 citations in OpenAlex.
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- Investigating the Role of Type I Interferon Signaling on Muscle Disease Using Mouse Models.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.Translational neurodegeneration · 2026Review
- Natural Killer Cell Dysregulation During ALS Disease Progression: A Gene Expression Analysis.Neurology open access · 2026Article
- Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026Review
- JAK/STAT signaling pathway inhibitors in neurodegenerative diseases: current status and future perspectives.Frontiers in aging neuroscience · 2026Review
- Gene expression signatures from whole blood predict amyotrophic lateral sclerosis case status and survival.Nature communications · 2025Article
- Review
- In Vitro Modeling of Natural Killer Cell Cytotoxicity to Inform Personalized ALS Therapeutics.Annals of clinical and translational neurology · 2025Article
- Tofacitinib extends survival in a mouse model of ALS through NK cell-independent mechanisms.Frontiers in immunology · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Peripheral Immune Profiles Predict ALS Progression in an Age- and Sex-Dependent Manner.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- The role of CD56Journal of neuroinflammation · 2024Review
- The Inflammatory Puzzle: Piecing together the Links between Neuroinflammation and Amyotrophic Lateral Sclerosis.Aging and disease · 2024Review
- Natural killer cells in the central nervous system.Cell communication and signaling : CCS · 2023Review
- Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis.Translational neurodegeneration · 2023Review
- miRNA analysis reveals novel dysregulated pathways in amyotrophic lateral sclerosis.Human molecular genetics · 2023Article
- Neutrophils: a subgroup of neglected immune cells in ALS.Frontiers in immunology · 2023Review
- Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1Frontiers in cellular neuroscience · 2023Article
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease with few therapeutic options. However, the immune system, including natural killer (NK) cells, is linked to ALS progression and may constitute a viable therapeutic ALS target. Tofacitinib is an FDA-approved immunomodulating small molecule which suppresses immune cell function by blocking proinflammatory cytokine signaling. This includes the cytokine IL-15 which is the primary cytokine associated with NK cell function and proliferation. However, the impact of tofacitinib on NK activation and cytotoxicity has not been thoroughly investigated, particularly in ALS. We therefore tested the ability of tofacitinib to suppress cytotoxicity and cytokine production in an NK cell line and in primary NK cells derived from control and ALS participants. We also investigated whether tofacitinib protected ALS neurons from NK cell cytotoxicity. Finally, we conducted a comprehensive pharmacokinetic study of tofacitinib in mice and tested the feasibility of administration formulated in chow. Success was assessed through the impact of tofacitinib on peripheral NK cell levels in mice. We found tofacitinib suppressed IL-15-induced activation as measured by STAT1 phosphorylation, cytotoxicity, pro-inflammatory gene expression, and pro-inflammatory cytokine secretion in both an NK cell line and primary NK cells. Furthermore, tofacitinib protected ALS neurons from NK cell-mediated cytotoxicity. In mice, we found tofacitinib bioavailability was 37% in both male and female mice; using these data we formulated mouse containing low and high doses of tofacitinib and found that the drug suppressed peripheral NK cell levels in a dose-dependent manner. These results demonstrate that tofacitinib can suppress NK cell function and may be a viable therapeutic strategy for ALS.
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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.