Evidence map›Paper›PMID 35385697›Full record

ArticleImmunity2022

Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and Gasdermin C.

Ming Zhao, Kaiqun Ren, Xiwen Xiong, Yue Xin, Yujie Zou, Jason C Maynard, Angela Kim, Alexander P Battist, Navya Koneripalli, Yusu Wang and 19 more

Erratum issuedOpen 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. An erratum has been issued. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
7.8field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026
    Review
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 7 institutions in 2 countries.

Ming ZhaoDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Kaiqun RenDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; College of Medicine, Hunan Normal University, Changsha, Hunan, China.
Xiwen XiongSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
Yue XinSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
Yujie ZouMOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Jason C MaynardDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
Angela KimDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Alexander P BattistDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Navya KoneripalliDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Yusu WangMOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Qianyue ChenMOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Ruyue XinMOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Chenyan YangSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
Rong HuangSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
Jiahui YuSchool of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
Zan HuangDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Zengdi ZhangDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Haiguang WangDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Daoyuan WangCollege of Medicine, Hunan Normal University, Changsha, Hunan, China.
Yihui XiaoCollege of Medicine, Hunan Normal University, Changsha, Hunan, China.
Oscar C SalgadoCenter for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Nicholas N JarjourCenter for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Kristin A HogquistCenter for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
Xavier S ReveloDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Alma L BurlingameDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA.
Xiang GaoMOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Jakob von MoltkeDepartment of Immunology, University of Washington School of Medicine, Seattle, Washington, USA.
Zhaoyu LinMOE Key Laboratory of Model Animals for Disease Study, State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China. Electronic address: linzy@nju.edu.cn.
Hai-Bin RuanDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA. Electronic address: hruan@umn.edu.
University of Minnesota Medical Center · USNanjing Drum Tower Hospital · CNXinxiang Medical University · CNHunan Normal University · CNUniversity of California, San Francisco · USUniversity of Minnesota · USUniversity of Washington · US

Funding

Sensing of helminths by tuft cellsDP2AI136596 · NIAID · UNIVERSITY OF WASHINGTON · PI VON MOLTKE, JAKOB H. · 2017 to 2017
$2.6M
Intestinal O-GlcNAc signaling and mucosal host defenseR01AI162791 · NIAID · UNIVERSITY OF MINNESOTA · PI Hai-Bin Ruan · 2022 to 2026
$2.4M
Protein O-GlcNAcylation in Regulatory T Cell FunctionR01AI139420 · NIAID · UNIVERSITY OF MINNESOTA · PI RUAN, HAI-BIN · 2019 to 2023
$2.3M
Mechanisms of B Cell Pathogenicity in Non-Alcoholic Fatty Liver DiseaseR01DK122056 · NIDDK · UNIVERSITY OF MINNESOTA · PI REVELO, XAVIER · 2019 to 2023
$1.7M
Intestinal O-GlcNAc signaling and mucosal host defenseR56AI162791 · NIAID · UNIVERSITY OF MINNESOTA · PI RUAN, HAI-BIN · 2021 to 2021
$484k
O-GlcNAc signaling enables the intestinal epithelial remodeling associated with type 2 immunityR21AI140109 · NIAID · UNIVERSITY OF MINNESOTA · PI RUAN, HAI-BIN · 2018 to 2019
$424k
NIAID NIH HHS DP2 AI136596NIAID NIH HHS R01 AI139420NIAID NIH HHS R01 AI162791NIAID NIH HHS R21 AI140109NIAID NIH HHS R56 AI162791NIDDK NIH HHS R01 DK122056
6 · The paper itself

Abstract

The epithelium is an integral component of mucosal barrier and host immunity. Following helminth infection, the intestinal epithelial cells secrete "alarmin" cytokines, such as interleukin-25 (IL-25) and IL-33, to initiate the type 2 immune responses for helminth expulsion and tolerance. However, it is unknown how helminth infection and the resulting cytokine milieu drive epithelial remodeling and orchestrate alarmin secretion. Here, we report that epithelial O-linked N-Acetylglucosamine (O-GlcNAc) protein modification was induced upon helminth infections. By modifying and activating the transcription factor STAT6, O-GlcNAc transferase promoted the transcription of lineage-defining Pou2f3 in tuft cell differentiation and IL-25 production. Meanwhile, STAT6 O-GlcNAcylation activated the expression of Gsdmc family genes. The membrane pore formed by GSDMC facilitated the unconventional secretion of IL-33. GSDMC-mediated IL-33 secretion was indispensable for effective anti-helminth immunity and contributed to induced intestinal inflammation. Protein O-GlcNAcylation can be harnessed for future treatment of type 2 inflammation-associated human diseases.

Indexed as

AlarminsIntestinal MucosaAcylationAnthelminticsBiomarkers, TumorCytokinesDNA-Binding ProteinsGasderminsHelminthiasisHumansHyperplasiaInflammationInterleukin-33MebendazoleN-AcetylglucosaminyltransferasesPore Forming Cytotoxic ProteinsAlarminsAnthelminticsBiomarkers, TumorCytokinesDNA-Binding ProteinsGasderminsGSDMC protein, humanInterleukin-33MebendazoleN-AcetylglucosaminyltransferasesO-GlcNAc transferasePore Forming Cytotoxic ProteinsSTAT6 protein, humanSTAT6 Transcription FactorcolitisGasdermingoblet cellIL-10IL-25IL-33O-GlcNAcOGTSTAT6Tuft cell

Identifiers

PMID35385697
PMCPMC9109499
OpenAlexW4224120095

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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.