Evidence map›Paper›PMID 26752231›Full record

ArticleAllergy2016

BCL-2 protects human and mouse Th17 cells from glucocorticoid-induced apoptosis.

J Banuelos, S Shin, Y Cao, B S Bochner, L Morales-Nebreda, G R S Budinger, L Zhou, S Li, J Xin, M W Lingen and 3 more

Open access · greenAbstract read
In one paragraph

Article in Allergy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 2 pooled it
4.4field-weighted citation impact, top 5% 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

45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.

  1. Pooled it
  2. Pharmacological Interventions for Glucocorticoid-Induced Osteoporosis: An Umbrella Review.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2023
    Pooled it
  3. Review
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  14. Genes · 2022
    Article
  15. The protective capability ofFrontiers in immunology · 2022
    Article
  16. Article
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  18. Review
  19. Article
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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 3 institutions in 2 countries.

J BanuelosDivision of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
S ShinDivision of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Y CaoDivision of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
B S BochnerDivision of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
L Morales-NebredaDivision of Pulmonary and Critical Care, Department of Medicine Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
G R S BudingerDivision of Pulmonary and Critical Care, Department of Medicine Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
L ZhouDepartments of Pathology and Immunology/Microbiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
S LiDepartment of Pharmacology and Human Tissue Resource Center, The University of Chicago, Chicago, IL, USA.
J XinDepartment of Pharmacology and Human Tissue Resource Center, The University of Chicago, Chicago, IL, USA.
M W LingenDepartment of Pharmacology and Human Tissue Resource Center, The University of Chicago, Chicago, IL, USA.
C DongBasic Medical Sciences, Tsinghua University, Beijing, China.
R P SchleimerDivision of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
N Z LuDivision of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Northwestern University · USUniversity of Chicago · USTsinghua University · CN

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Systems Genetics Approach to Gene Discovery in Chronic RhinosinusitisU19AI106683 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SCHLEIMER, ROBERT P · 2014 to 2017
$7.9M
Targeting Siglec-8/Siglec-F Reduce Allergic Responses In Vitro and In VivoR01AI072265 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BOCHNER, BRUCE S · 2007 to 2017
$3.9M
Glucocorticosteroid Action In Inflammatory DiseaseR37HL068546 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SCHLEIMER, ROBERT P · 2009 to 2018
$3.5M
AhR activation in Th17 and Treg cell differentiationR01AI089954 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ZHOU, LIANG · 2010 to 2014
$1.9M
ROLE OF AHR IN T LYMPHOCYTE DEVELOPMENT AND FUNCTIONR01DK105562 · NIDDK · UNIVERSITY OF FLORIDA · PI ZHOU, LIANG · 2015 to 2019
$1.8M
Glucocorticoids and glucocorticoid receptor translational isoformsR21AI113935 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LU, NICK · 2014 to 2015
$425k
NCI NIH HHS P30 CA060553NHLBI NIH HHS R37 HL068546NIAID NIH HHS R01 AI072265NIAID NIH HHS R01 AI089954NIAID NIH HHS R21 AI113935NIAID NIH HHS U19 AI106683NIDDK NIH HHS R01 DK105562
6 · The paper itself

Abstract

backgroundGlucocorticoid resistance has been associated with Th17-driven inflammation, the mechanisms of which are not clear. We determined whether human and mouse Th17 cells are resistant to glucocorticoid-induced apoptosis.

methodsFreshly isolated human blood Th17 cells and in vitro differentiated Th17 cells from IL-17F red fluorescent protein reporter mice were treated with dexamethasone, a potent glucocorticoid. Apoptosis was measured using annexin V and DAPI staining. Screening of apoptosis genes was performed using the apoptosis PCR array. Levels of molecules involved in apoptosis were measured using quantitative RT-PCR, flow cytometry, and Western blotting. Knockdown of BCL-2 in murine Th17 cells was performed via retroviral transduction. Cytokines were measured using ELISA. A murine Th17-driven severe asthma model was examined for Th17 glucocorticoid sensitivity in vivo.

resultsHuman and mouse Th17 cells and mouse Th2 cells were resistant to glucocorticoid-induced apoptosis. Th17 cells had glucocorticoid receptors levels comparable to those in other T effectors cells. Th17 cells had high levels of BCL-2, knockdown of which sensitized Th17 cells to dexamethasone-induced apoptosis. Production of IL-22, but not IL-17A and IL-17F, was suppressed by glucocorticoids. STAT3 phosphorylation in Th17 cells was insensitive to glucocorticoid inhibition. Lung Th17 cells in the murine severe asthma model were enhanced, rather than suppressed, by glucocorticoids.

conclusionTh17 cells are resistant to glucocorticoid-induced apoptosis and cytokine suppression, at least in part due to high levels of BCL-2. These findings support a role of Th17 cells in glucocorticoid-resistant inflammatory conditions such as certain endotypes of asthma.

Indexed as

Genes, bcl-2AnimalsApoptosisAsthmaBiomarkersCytokinesDisease Models, AnimalDrug ResistanceGene ExpressionGene Knockdown TechniquesGlucocorticoidsHumansImmunophenotypingLungMiceTh17 CellsBiomarkersCytokinesGlucocorticoidsapoptosisasthmaglucocorticoidsT cellsTh17 cells

Identifiers

PMID26752231
PMCPMC4844778
OpenAlexW2235741511

What OpenQuestion holds

Textmetadata
LicenceTDM
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.