Evidence map›Paper›PMID 34934928›Full record

ArticleiScience2021

Hydroxychloroquine inhibits the mitochondrial antioxidant system in activated T cells.

Man Lyang Kim, Melinda Y Hardy, Laura E Edgington-Mitchell, Sri H Ramarathinam, Shan Zou Chung, Amy K Russell, Iain Currie, Brad E Sleebs, Anthony W Purcell, Jason A Tye-Din and 1 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2021. 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
2.1field-weighted citation impact, top 12% 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, 22 citations in OpenAlex.

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  13. The Role of Autophagy in the Function of CD4Frontiers in pharmacology · 2022
    Review
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

11 authors at 6 institutions in 2 countries.

Man Lyang KimWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Melinda Y HardyWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Laura E Edgington-MitchellDepartment of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3052, Australia.
Sri H RamarathinamInfection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University, Clayton, VIC 3800, Australia.
Shan Zou ChungInfection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University, Clayton, VIC 3800, Australia.
Amy K RussellWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Iain CurrieWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Brad E SleebsWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Anthony W PurcellInfection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University, Clayton, VIC 3800, Australia.
Jason A Tye-DinWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Ian P WicksWalter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
University of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AUMonash University · AUAustralian Regenerative Medicine Institute · AUNew York University · USThe Royal Melbourne Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although hydroxychloroquine (HCQ) has long been used to treat autoimmune diseases, its mechanism of action remains poorly understood. In CD4 T-cells, we found that a clinically relevant concentration of HCQ inhibited the mitochondrial antioxidant system triggered by TCR crosslinking, leading to increased mitochondrial superoxide, impaired activation-induced autophagic flux, and reduced proliferation of CD4 T-cells. In antigen-presenting cells, HCQ also reduced constitutive activation of the endo-lysosomal protease legumain and toll-like receptor 9, thereby reducing cytokine production, but it had little apparent impact on constitutive antigen processing and peptide presentation. HCQ's effects did not require endo-lysosomal pH change, nor impaired autophagosome-lysosome fusion. We explored the clinical relevance of these findings in patients with celiac disease-a prototypic CD4 T-cell-mediated disease-and found that HCQ limits

Indexed as

Immune systemMolecular biologyProteomics

Identifiers

PMID34934928
PMCPMC8661543
OpenAlexW3217312688

What OpenQuestion holds

Textmetadata
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.