Evidence map›Paper›PMID 32539713›Full record

ArticleBMC immunology2020

JAK inhibitors impair GM-CSF-mediated signaling in innate immune cells.

Yuya Fujita, Naoki Matsuoka, Jumpei Temmoku, Makiko Furuya-Yashiro, Tomoyuki Asano, Shuzo Sato, Haruki Matsumoto, Hiroshi Watanabe, Hideko Kozuru, Hiroshi Yatsuhashi and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 20% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  6. Macrophage re-programming by JAK inhibitors relies on MAFB.Cellular and molecular life sciences : CMLS · 2024
    Article
  7. Dendritic cells resist to disulfiram-induced cytotoxicity, but reduced interleukin-12/23(p40) production.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023
    Article
  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Yuya FujitaDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Naoki MatsuokaDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Jumpei TemmokuDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Makiko Furuya-YashiroDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Tomoyuki AsanoDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Shuzo SatoDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Haruki MatsumotoDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Hiroshi WatanabeDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
Hideko KozuruClinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1 Omura, Nagasaki, 856-8562, Japan.
Hiroshi YatsuhashiClinical Research Center, NHO Nagasaki Medical Center, Kubara 2-1001-1 Omura, Nagasaki, 856-8562, Japan.
Atsushi KawakamiDepartment of Immunology and Rheumatology, Unit of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto1-7-1, Nagasaki, 852-8501, Japan.
Kiyoshi MigitaDepartment of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan. migita@fmu.ac.jp.
Fukushima Medical University · JPNagasaki Medical Center · JPNagasaki University · JP

Funding

Japan Agency for Medical Research and Development 2019-221
6 · The paper itself

Abstract

backgroundInnate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells.

resultsTreatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils.

conclusionWe conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidAzetidinesCell LineGranulocyte-Macrophage Colony-Stimulating FactorHeterocyclic Compounds, 3-RingHumansImmunity, InnateJanus Kinase 2Janus Kinase InhibitorsNeutrophilsPiperidinesPurinesPyrazolesPyrimidinesSignal TransductionAntirheumatic AgentsAzetidinesbaricitinibGranulocyte-Macrophage Colony-Stimulating FactorHeterocyclic Compounds, 3-RingJanus Kinase 2Janus Kinase InhibitorsPiperidinesPurinesPyrazolesPyrimidinesSTAT5 Transcription FactorSulfonamidestofacitinibupadacitinibBaricitinibGM-CSFIL-1βJanus kinasesRheumatoid arthritisTofacitinibUpadacitinib

Identifiers

PMID32539713
PMCPMC7296727
OpenAlexW3034640595

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.