Evidence map›Paper›PMID 37582366›Full record

ArticleNeuron2023

A novel immune modulator IM33 mediates a glia-gut-neuronal axis that controls lifespan.

Wangchao Xu, Justin Rustenhoven, Christopher A Nelson, Taitea Dykstra, Aura Ferreiro, Zachary Papadopoulos, Carey-Ann D Burnham, Gautam Dantas, Daved H Fremont, Jonathan Kipnis

Open access · bronzeAbstract read
In one paragraph

Article in Neuron, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 13% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Sleep regulation inFrontiers in neuroscience · 2026
    Review
  5. Immunomodulatory Effects ofCurrent issues in molecular biology · 2025
    Review
  6. Microbiome: A Key Regulator of Body-Brain Interactions.Advances in experimental medicine and biology · 2025
    Review
  7. Article
  8. Article
  9. Article
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

10 authors at 2 institutions in 2 countries.

Wangchao XuBrain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. Electronic address: xu.w@wustl.edu.
Justin RustenhovenBrain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand; Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
Christopher A NelsonDepartment of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Taitea DykstraBrain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Aura FerreiroThe Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Zachary PapadopoulosBrain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Carey-Ann D BurnhamDepartment of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Gautam DantasDepartment of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Daved H FremontDepartment of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Jonathan KipnisBrain Immunology and Glia (BIG) Center, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Neuroscience Graduate Program, School of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. Electronic address: kipnis@wustl.edu.
Washington University in St. Louis · USUniversity of Auckland · NZ

Funding

Resource Component: Acquisition, maintenance and distribution of Drosophila stocksP40OD018537 · OD · TRUSTEES OF INDIANA UNIVERSITY · PI Cale Whitworth · 2014 to 2026
$13.5M
Neural code of the immune responsesDP1AT010416 · NCCIH · WASHINGTON UNIVERSITY · PI KIPNIS, JONATHAN · 2018 to 2022
$5.6M
Tunable therapeutic modulation of the gut microbiome by engineered probioticsR01AT009741 · NCCIH · WASHINGTON UNIVERSITY · PI DANTAS, GAUTAM, MOON, TAE SEOK · 2018 to 2022
$3.5M
NCCIH NIH HHS DP1 AT010416NCCIH NIH HHS R01 AT009741NIAID NIH HHS HHSN272201700060CNIH HHS P40 OD018537
6 · The paper itself

Abstract

Aging is a complex process involving various systems and behavioral changes. Altered immune regulation, dysbiosis, oxidative stress, and sleep decline are common features of aging, but their interconnection is poorly understood. Using Drosophila, we discover that IM33, a novel immune modulator, and its mammalian homolog, secretory leukocyte protease inhibitor (SLPI), are upregulated in old flies and old mice, respectively. Knockdown of IM33 in glia elevates the gut reactive oxygen species (ROS) level and alters gut microbiota composition, including increased Lactiplantibacillus plantarum abundance, leading to a shortened lifespan. Additionally, dysbiosis induces sleep fragmentation through the activation of insulin-producing cells in the brain, which is mediated by the binding of Lactiplantibacillus plantarum-produced DAP-type peptidoglycan to the peptidoglycan recognition protein LE (PGRP-LE) receptor. Therefore, IM33 plays a role in the glia-microbiota-neuronal axis, connecting neuroinflammation, dysbiosis, and sleep decline during aging. Identifying molecular mediators of these processes could lead to the development of innovative strategies for extending lifespan.

Indexed as

Drosophila ProteinsLongevitySecretory Leukocyte Peptidase InhibitorAnimalsDrosophilaDysbiosisMiceNeurogliaDrosophila ProteinsSecretory Leukocyte Peptidase InhibitorSlpi protein, mousebrain-gut axisDrosophilaglia-gut axisIM33longevityneuroimmunology

Identifiers

PMID37582366
PMCPMC10592285
OpenAlexW4385813766

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.