Evidence map›Paper›PMID 41495316›Full record

ArticleNature immunology2026

The IL17REL gene encodes a decoy receptor of IL-17 family cytokines to control gut inflammation.

Qi Li, Xiaoyu Li, Yunwei Lou, Yingying Xing, Wei Yan, Yuan Chen, Guohong Hu, Xinyang Song, Zhanju Liu, Tao Yang and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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.

Qi LiShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Xiaoyu LiDepartment of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Yunwei LouShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yingying XingShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Wei YanShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Yuan ChenSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Guohong HuShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-2980-5166
Xinyang SongKey Laboratory of Multi-Cell Systems, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-3422-6927
Zhanju LiuDepartment of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-0326-543X
Tao YangShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. yangtao@sinh.ac.cn.ORCID http://orcid.org/0000-0003-0234-3560
Youcun QianShanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. ycqian@sinh.ac.cn.ORCID http://orcid.org/0000-0002-2269-888X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32030039
6 · The paper itself

Abstract

The IL17REL gene locus has been associated with susceptibility to inflammatory bowel disease (IBD). However, whether it encodes a functional protein and whether its IBD risk variants causally contribute to disease pathogenesis remain unknown. Here, we demonstrated that IL17REL encodes a decoy receptor capable of binding interleukin-17 (IL-17) family cytokines and suppressing intestinal inflammation. By contrast, proteins encoded by IBD-associated IL17REL variants lacked this function. We also showed that TGFβ1 induced IL17REL transcription, and its expression positively correlated with TGFB1 levels in IBD. Mechanistically, the IL-17REL protein competed with IL-17RA for IL-17A binding, an ability that is lost in the mutant form. Knock-in of IL17REL in mice alleviated 2,4,6-trinitrobenzene sulfonic acid-induced colitis, whereas knock-in of an IBD-associated IL17REL mutant did not. In addition, therapeutic administration of IL-17REL protein alleviated colitis symptoms. Together, these findings implicate IL-17REL variants in the pathogenesis of IBD and highlight IL-17REL as a potential therapeutic target.

Indexed as

ColitisInflammatory Bowel DiseasesInterleukin-17AnimalsDisease Models, AnimalGene Knock-In TechniquesHumansInflammationMiceMice, Inbred C57BLMice, KnockoutReceptors, Interleukin-17Transforming Growth Factor beta1Trinitrobenzenesulfonic AcidInterleukin-17Receptors, Interleukin-17Transforming Growth Factor beta1Trinitrobenzenesulfonic Acid

Identifiers

PMID41495316

What OpenQuestion holds

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Registered trials

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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.