Evidence map›Paper›PMID 40434419›Full record

ArticleThe Journal of experimental medicine2025

Functional targeting of ILC2s and ILC3s reveals selective roles in intestinal fibrosis and homeostasis.

Ahmed Kabil, Natalia Nayyar, Chengxi Xu, Julyanne Brassard, Lesley A Hill, Samuel B Shin, Sameeksha Chopra, Bernard Lo, Yicong Li, Mya Bal and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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  6. 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

15 authors.

Ahmed KabilSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0001-7063-6504
Natalia NayyarSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0009-0007-9170-3877
Chengxi XuSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0009-0000-5041-3004
Julyanne BrassardSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0001-9093-674X
Lesley A HillDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada.ORCID 0000-0001-6609-1935
Samuel B ShinSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0001-8472-5620
Sameeksha ChopraSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0001-5496-7610
Bernard LoDepartment of Pathology and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.ORCID 0009-0001-4637-6121
Yicong LiSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0002-8368-7594
Mya BalSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0009-0001-8187-6594
Marine TheretSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0002-8059-8756
Fabio M V RossiSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0002-0368-2620
T Michael UnderhillSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0003-3048-9102
Michael R HughesSchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0002-7925-6070
Kelly M McNagnySchool of Biomedical Engineering, University of British Columbia , Vancouver, Canada.ORCID 0000-0003-4737-3499

Funding

Canadian Microbiome Team Grants MRT168044Canadian Microbiome Team Grants MRT-168048CIHR PJT-4488212CIHR PJT-518208Michael Smith Foundation of Health ResearchNatural Sciences and Engineering Research Council of Canada
6 · The paper itself

Abstract

Innate lymphoid cells (ILCs) are long-lived, tissue-resident cell analogs to T helper subsets that lack antigen-specific receptors. Understanding the roles of specific ILCs in chronic inflammation and fibrosis has been limited by inadequate tools for selective targeting. Here, we used Il17rb-CreERT2-eGFP and Rorc-Cre strains to selectively delete RORα in ILC2s and ILC3/Th17 cells, respectively. RORα deletion in ILC2s caused significant loss of gastrointestinal ILC2s, increased ILC3 abundance, elevated Th17-type responses, and heightened susceptibility to Crohn's disease-like fibrosis. Conversely, RORα deletion in ILC3/Th17 cells reduced IL-17 production, protecting against fibrosis. Using isolithocholic acid (isoLCA), a microbial secondary bile acid and RORγt inverse agonist, we confirmed the role of ILC3s/Th17 cells in fibrosis. In RORγt reporter and Th17-deficient Rag1-/- mice, isoLCA reduced IL-17 production by ILC3s and attenuated intestinal fibrosis by dampening RORγt-dependent ILC3/Th17 responses. These findings reveal a novel interplay between ILC2s and ILC3s in gut homeostasis and demonstrate the therapeutic potential of targeting RORγt in ILC3s as a strategy for preventing fibrosis.

Indexed as

HomeostasisImmunity, InnateIntestinesLymphocytesAnimalsCrohn DiseaseFibrosisInterleukin-17MiceMice, Inbred C57BLMice, KnockoutNuclear Receptor Subfamily 1, Group F, Member 1Nuclear Receptor Subfamily 1, Group F, Member 3Th17 CellsInterleukin-17Nuclear Receptor Subfamily 1, Group F, Member 1Nuclear Receptor Subfamily 1, Group F, Member 3Rora protein, mouse

Identifiers

PMID40434419
PMCPMC12118370

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.