Evidence map›Paper›PMID 30667372›Full record

ArticleThe Journal of clinical investigation2019

Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability.

Sam C Nalle, Li Zuo, Ma Lora Drizella M Ong, Gurminder Singh, Alicia M Worthylake, Wangsun Choi, Mario Cabrero Manresa, Anna P Southworth, Karen L Edelblum, Gregory J Baker and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

54 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease.Laboratory investigation; a journal of technical methods and pathology · 2026
    Article
  8. Review
  9. Loss of GLP-2R signaling in Glp2rMolecular metabolism · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. 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

13 authors at 4 institutions in 2 countries.

Sam C NalleDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Li ZuoDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ma Lora Drizella M OngDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Gurminder SinghDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Alicia M WorthylakeDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Wangsun ChoiDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Mario Cabrero ManresaDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Anna P SouthworthDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Karen L EdelblumDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Gregory J BakerLaboratory of Systems Pharmacology, Harvard Medical School, Harvard Program in Therapeutic Science, Boston, Massachusetts, USA.
Nora E JosephDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Peter A SavageDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Jerrold R TurnerDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Brigham and Women's Hospital · USUniversity of Chicago · USHarvard University · USRutgers, The State University of New Jersey · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
ZO-1-MEDIATED PROTEIN INTERACTIONS: REGULATORS AND INTEGRATORS OF DIVERSE EPITHELIAL FUNCTIONS IN HEALTH AND DISEASER01DK061931 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2001 to 2026
$15.0M
Therapeutic targeting of protein interactions to reverse MLCK1-mediated intestinal barrier loss and ameliorate disease.R01DK068271 · NIDDK · UNIVERSITY OF CHICAGO · PI JERROLD R. TURNER · 2005 to 2026
$11.3M
Translational Approaches to Develop Drug Therapy for DiarrheaR24DK099803 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI DONOWITZ, MARK · 2014 to 2019
$8.9M
Function of Aire-dependent regulatory T cells in immune toleranceR01AI110507 · NIAID · UNIVERSITY OF CHICAGO · PI SAVAGE, PETER AIDAN · 2015 to 2019
$1.7M
NIAID NIH HHS R01 AI110507NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK061931NIDDK NIH HHS R01 DK068271NIDDK NIH HHS R24 DK099803
6 · The paper itself

Abstract

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation (HSCT) that affects multiple organs. GVHD-associated intestinal damage can be separated into two distinct phases, initiation and propagation, which correspond to conditioning-induced damage and effector T cell activation and infiltration, respectively. Substantial evidence indicates that intestinal damage induced by pretransplant conditioning is a key driver of GVHD initiation. Here, we aimed to determine the impact of dysregulated intestinal permeability on the subsequent GVHD propagation phase. The initiation phase of GVHD was unchanged in mice lacking long MLCK (MLCK210), an established regulator of epithelial tight junction permeability. However, MLCK210-deficient mice were protected from sustained barrier loss and exhibited limited GVHD propagation, as indicated by reduced histopathology, fewer CD8+ effector T cells in the gut, and improved overall survival. Consistent with these findings, intestinal epithelial MLCK210 expression and enzymatic activity were similarly increased in human and mouse GVHD biopsies. Intestinal epithelial barrier loss mediated by MLCK210 is therefore a key driver of the GVHD propagation. These data suggest that inhibition of MLCK210-dependent barrier regulation may be an effective approach to limiting GVHD progression.

Indexed as

Hematopoietic Stem Cell TransplantationAllograftsAnimalsCD8-Positive T-LymphocytesFemaleGraft vs Host DiseaseIntestinal MucosaMiceMice, Inbred BALB CMyosin-Light-Chain KinaseTight JunctionsMyosin-Light-Chain KinaseGastroenterologyOncologyStem cell transplantationT cellsTight junctions

Identifiers

PMID30667372
PMCPMC6355225
OpenAlexW2911901386

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.