Evidence map›Paper›PMID 34982959›Full record

ArticleImmunity2022

Disruption of the IL-33-ST2-AKT signaling axis impairs neurodevelopment by inhibiting microglial metabolic adaptation and phagocytic function.

Danyang He, Heping Xu, Huiyuan Zhang, Ruihan Tang, Yangning Lan, Ruxiao Xing, Shaomin Li, Elena Christian, Yu Hou, Paul Lorello and 10 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 2 pooled it
13.5field-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

102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 162 citations in OpenAlex.

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42 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

20 authors at 3 institutions in 2 countries.

Danyang HeEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Institute of Basic Medical Science, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: hedanyang@westlake.edu.cn.
Heping XuSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Institute of Basic Medical Science, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Huiyuan ZhangEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ruihan TangEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yangning LanSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Institute of Basic Medical Science, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
Ruxiao XingSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Institute of Basic Medical Science, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
Shaomin LiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Elena ChristianKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yu HouEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Paul LorelloMouse Behavior Core, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Barbara CaldaroneMouse Behavior Core, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jiarui DingKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Lan NguyenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Danielle DionneKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pratiksha ThakoreKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexandra SchnellEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jun R HuhEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Orit Rozenblatt-RosenKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Aviv RegevKlarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: aregev@broadinstitute.org.
Vijay K KuchrooEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: vkuchroo@rics.bwh.harvard.edu.
Broad Institute · USBrigham and Women's Hospital · USWestlake University · CN

Funding

Neuroimmune interactions regulate development of allergic inflammationR01AI139536 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI KUCHROO, VIJAY K. · 2018 to 2022
$2.9M
Neuroimmune interactions regulate development of allergic inflammationR37AI139536 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI VIJAY K. KUCHROO · 2024 to 2026
$1.8M
NIAID NIH HHS R01 AI139536NIAID NIH HHS R37 AI139536
6 · The paper itself

Abstract

To accommodate the changing needs of the developing brain, microglia must undergo substantial morphological, phenotypic, and functional reprogramming. Here, we examined whether cellular metabolism regulates microglial function during neurodevelopment. Microglial mitochondria bioenergetics correlated with and were functionally coupled to phagocytic activity in the developing brain. Transcriptional profiling of microglia with diverse metabolic profiles revealed an activation signature wherein the interleukin (IL)-33 signaling axis is associated with phagocytic activity. Genetic perturbation of IL-33 or its receptor ST2 led to microglial dystrophy, impaired synaptic function, and behavioral abnormalities. Conditional deletion of Il33 from astrocytes or Il1rl1, encoding ST2, in microglia increased susceptibility to seizures. Mechanistically, IL-33 promoted mitochondrial activity and phagocytosis in an AKT-dependent manner. Mitochondrial metabolism and AKT activity were temporally regulated in vivo. Thus, a microglia-astrocyte circuit mediated by the IL-33-ST2-AKT signaling axis supports microglial metabolic adaptation and phagocytic function during early development, with implications for neurodevelopmental and neuropsychiatric disorders.

Indexed as

AnimalsBehavior, AnimalDisease SusceptibilityElectrical SynapsesEnergy MetabolismHumansInterleukin-1 Receptor-Like 1 ProteinInterleukin-33MiceMice, KnockoutMicrogliaMitochondriaNeurogenesisOncogene Protein v-aktPhagocytosisSeizuresIl1rl1 protein, mouseIl33 protein, mouseInterleukin-1 Receptor-Like 1 ProteinInterleukin-33Oncogene Protein v-aktbioenergeneticsIL-33microglianeurodevelopmentphagocytosisseizuresynapse

Identifiers

PMID34982959
PMCPMC9074730
OpenAlexW4206447661

What OpenQuestion holds

Textmetadata
LicenceTDM
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.