Evidence map›Paper›PMID 42153603›Full record

ArticleEuropean journal of immunology2026

A Novel PTPN2 Isoform Differentially Regulates Immune Response.

Xiaoguang Li, Fedik Rahimov, Rui Wang, Lei Gao, Renze Ma, Tiankai Han, Yingtao Bi, Freidrich Cruz, Jing Wang, Shaun Grosskurth and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

17 authors.

Xiaoguang LiImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.ORCID 0000-0003-0926-6561
Fedik RahimovGenomics Research Center, AbbVie, Inc., North Chicago, Illinois, USA.
Rui WangImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Lei GaoImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Renze MaSmall Molecule Therapeutics & Platform Technologies, AbbVie, Inc., North Chicago, Illinois, USA.
Tiankai HanImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Yingtao BiAbbVie Bioresearch Center, Worcester, Massachusetts, USA.
Freidrich CruzImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Jing WangGenomics Research Center, AbbVie, Inc., North Chicago, Illinois, USA.
Shaun GrosskurthImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Elizabeth AsqueGenomics Research Center, AbbVie, Inc., North Chicago, Illinois, USA.
Jesus Paez-CortezImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Marc C LevesqueImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Nancy E CrosbieAbbVie Bioresearch Center, Worcester, Massachusetts, USA.
Timothy RadstakeImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Amlan BiswasImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.
Kanstantsin KatlinskiImmunology Discovery Research, AbbVie, Inc., Cambridge, Massachusetts, USA.

Funding

AbbVie Inc.
6 · The paper itself

Abstract

Genome-wide association studies implicate the PTPN2 gene locus (18p11.21) in risk for several autoimmune diseases, including inflammatory bowel disease. Through genetic fine mapping, we identified the single-nucleotide polymorphism rs80262450 in the PTPN2 gene as the putative causal variant. Analysis of GTEx tissue samples and genetically engineered myeloid cell lines carrying risk and nonrisk alleles of rs80262450 demonstrated increased expression of the PTPN2 splice isoform 4 (PTPN2.4), suggesting that the rs80262450 enhances disease susceptibility by favoring production of PTPN2.4. Furthermore, we found that PTPN2.4 contains a nuclear export sequence (NES) that leads to its retention in the cytoplasm. Differential localization of PTPN2.4 isoform results in a distinct protein binding profile revealed by mass-spectrometry analysis, and its overexpression increased TNF-α. PTPN2.4 knockdown reduced pro-inflammatory cytokines in human macrophages. Mutations within the NES motif abolished the unique localization and function of PTPN2.4. Lastly, increased expression of PTPN2.4 was found in Crohn's disease tissues, demonstrating its involvement in the disease. Together, we identified the pathogenic isoform PTPN2.4 as a novel driver of intestinal inflammation and a potential target to attenuate inflammation in IBD.

Indexed as

Crohn DiseaseProtein Tyrosine Phosphatase, Non-Receptor Type 2Genetic Predisposition to DiseaseGenome-Wide Association StudyHumansMacrophagesPolymorphism, Single NucleotideProtein IsoformsTumor Necrosis Factor-alphaProtein IsoformsProtein Tyrosine Phosphatase, Non-Receptor Type 2PTPN2 protein, humanTumor Necrosis Factor-alphaimmune responseinflammationInflammatory bowel diseasePTPN2 isoformsingle nucleotide polymorphismtherapeutic targets

Identifiers

PMID42153603
PMCPMC13185683

What OpenQuestion holds

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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.