Evidence map›Paper›PMID 31619589›Full record

ArticleJCI insight2019

STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice.

Wei Cai, Xuejiao Dai, Jie Chen, Jingyan Zhao, Mingyue Xu, Lili Zhang, Boyu Yang, Wenting Zhang, Marcelo Rocha, Toshimasa Nakao and 5 more

Open access · goldAbstract readCase Reports
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.

0numbers the graph read from it
0cells of the map it votes in
183citing papers in PubMed
11.5field-weighted citation impact, top 1% 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

183 citing papers in PubMed, 303 citations in OpenAlex.

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  6. Brain-muscle axis regulation of neuroinflammation and sarcopenia in Parkinson's disease: the bridging role of lactylation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  17. Phagocytosis is crucial for brain repair.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Article
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123 more citing papers are in PubMed but not listed here.

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

15 authors at 2 institutions in 1 country.

Wei CaiPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Xuejiao DaiPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jie ChenPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jingyan ZhaoPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Mingyue XuPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Lili ZhangPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Boyu YangPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Wenting ZhangPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Marcelo RochaPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Toshimasa NakaoT.E. Starzl Transplantation Institute and Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Julia KoflerDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Yejie ShiPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
R Anne StetlerPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Xiaoming HuPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Jun ChenPittsburgh Institute of Brain Disorders and Recovery, and Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh · USUniversity of Pittsburgh Medical Center · US

Funding

TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KOFLER, JULIA K · 1985 to 2019
$43.0M
Immunomodulation of white matter integrity after strokeR01NS092618 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HU, XIAOMING · 2015 to 2020
$1.7M
White matter restoration and functional recovery after experimental strokeR01NS095671 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHEN, JUN · 2015 to 2020
$1.7M
ImageStreamX MarkIIS10OD019942 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BORGHESI, LISA · 2015 to 2015
$543k
Interleukin-33 as an immune therapy for strokeI01BX003651 · VA · VETERANS HEALTH ADMINISTRATION · PI HU, XIAOMING · 2019 to 2023
–
BLRD VA I01 BX003377BLRD VA I01 BX003651NIA NIH HHS P50 AG005133NIH HHS S10 OD019942NINDS NIH HHS R01 NS092618NINDS NIH HHS R01 NS095671
6 · The paper itself

Abstract

Efferocytosis, or phagocytic clearance of dead/dying cells by brain-resident microglia and/or infiltrating macrophages, is instrumental for inflammation resolution and restoration of brain homeostasis after stroke. Here, we identify the signal transducer and activator of transcription 6/arginase1 (STAT6/Arg1) signaling axis as a potentially novel mechanism that orchestrates microglia/macrophage responses in the ischemic brain. Activation of STAT6 was observed in microglia/macrophages in the ischemic territory in a mouse model of stroke and in stroke patients. STAT6 deficiency resulted in reduced clearance of dead/dying neurons, increased inflammatory gene signature in microglia/macrophages, and enlarged infarct volume early after experimental stroke. All of these pathological changes culminated in an increased brain tissue loss and exacerbated long-term functional deficits. Combined in vivo analyses using BM chimeras and in vitro experiments using microglia/macrophage-neuron cocultures confirmed that STAT6 activation in both microglia and macrophages was essential for neuroprotection. Adoptive transfer of WT macrophages into STAT6-KO mice reduced accumulation of dead neurons in the ischemic territory and ameliorated brain infarction. Furthermore, decreased expression of Arg1 in STAT6-/- microglia/macrophages was responsible for impairments in efferocytosis and loss of antiinflammatory modality. Our study suggests that efferocytosis via STAT6/Arg1 modulates microglia/macrophage phenotype, accelerates inflammation resolution, and improves stroke outcomes.

Indexed as

Aged, 80 and overAnimalsArginaseBrainBrain InfarctionCells, CulturedDisease Models, AnimalFemaleHumansMacrophagesMaleMiceMicrogliaNeuronsPhagocytosisPrimary Cell CultureARG1 protein, humanArg1 protein, mouseArginaseSTAT6 protein, humanStat6 protein, mouseSTAT6 Transcription FactorInflammationNeuroscienceStroke

Identifiers

PMID31619589
PMCPMC6824303
OpenAlexW2980464820

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.