Evidence map›Paper›PMID 24402311›Full record

ArticleInternational immunology2014

IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation.

Richard Metz, Courtney Smith, James B DuHadaway, Phillip Chandler, Babak Baban, Lauren M F Merlo, Elizabeth Pigott, Martin P Keough, Sonja Rust, Andrew L Mellor and 3 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in International immunology, 2014. 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 109 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 1 pooled it
7.4field-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

109 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.

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  12. Tryptophan catabolism via the kynurenine pathway regulates infection and inflammation: from mechanisms to biomarkers and therapies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Review
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49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Richard MetzNew Link Genetics Corporation, Ames, IA 50010, USA.
Courtney SmithLankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
James B DuHadawayLankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
Phillip ChandlerImmunotherapy Center, Georgia Regents University, Augusta, GA 30912, USA.
Babak BabanImmunotherapy Center, Georgia Regents University, Augusta, GA 30912, USA.
Lauren M F MerloLankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
Elizabeth PigottLankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
Martin P KeoughLankenau Institute for Medical Research, Wynnewood, PA 19096, USA.
Sonja RustNew Link Genetics Corporation, Ames, IA 50010, USA.
Andrew L MellorImmunotherapy Center, Georgia Regents University, Augusta, GA 30912, USA.
Laura Mandik-NayakLankenau Institute for Medical Research, Wynnewood, PA 19096, USA Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Alexander J MullerLankenau Institute for Medical Research, Wynnewood, PA 19096, USA Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
George C PrendergastLankenau Institute for Medical Research, Wynnewood, PA 19096, USA Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA Department of Pathology, Anatomy and Cell Biology, Jefferson Medical School, Thomas Jefferson University, Philadelphia, PA 19107, USA prendergast@limr.org.
Lankenau Institute for Medical Research · USAugusta University · USNewLink Genetics (United States) · USThomas Jefferson University · US

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI DANIEL P SILVER · 1995 to 2026
$94.8M
NCI NIH HHS P30 CA056036
6 · The paper itself

Abstract

IDO2 is implicated in tryptophan catabolism and immunity but its physiological functions are not well established. Here we report the characterization of mice genetically deficient in IDO2, which develop normally but exhibit defects in IDO-mediated T-cell regulation and inflammatory responses. Construction of this strain was prompted in part by our discovery that IDO2 function is attenuated in macrophages from Ido1 (-/-) mice due to altered message splicing, generating a functional mosaic with implications for interpreting findings in Ido1 (-/-) mice. No apparent defects were observed in Ido2 (-/-) mice in embryonic development or hematopoietic differentiation, with wild-type profiles documented for kynurenine in blood serum and for immune cells in spleen, lymph nodes, peritoneum, thymus and bone marrow of naive mice. In contrast, upon immune stimulation we determined that IDO1-dependent T regulatory cell generation was defective in Ido2 (-/-) mice, supporting Ido1-Ido2 genetic interaction and establishing a functional role for Ido2 in immune modulation. Pathophysiologically, both Ido1 (-/-) and Ido2 (-/-) mice displayed reduced skin contact hypersensitivity responses, but mechanistic distinctions were apparent, with only Ido2 deficiency associated with a suppression of immune regulatory cytokines that included GM-CSF, G-CSF, IFN-γ, TNF-α, IL-6 and MCP-1/CCL2. Different contributions to inflammation were likewise indicated by the finding that Ido2 (-/-) mice did not phenocopy Ido1 (-/-) mice in the reduced susceptibility of the latter to inflammatory skin cancer. Taken together, our results offer an initial glimpse into immune modulation by IDO2, revealing its genetic interaction with IDO1 and distinguishing its non-redundant contributions to inflammation.

Indexed as

9,10-Dimethyl-1,2-benzanthraceneAnimalsCarcinogensCytokinesDendritic CellsFemaleGene Expression RegulationIndoleamine-Pyrrole 2,3,-DioxygenaseInflammationKynurenineLymphocyte Culture Test, MixedMaleMiceMice, KnockoutPapillomaSignal Transduction4-O-methyl-12-O-tetradecanoylphorbol 13-acetate9,10-Dimethyl-1,2-benzanthraceneCarcinogensCytokinesIDO1 protein, mouseIDO2 protein, mouseIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineTetradecanoylphorbol Acetateadaptive immunitycontact hypersensitivityinflammationtolerance

Identifiers

PMID24402311
PMCPMC4432394
OpenAlexW2123824227

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.