Evidence map›Paper›PMID 18209088›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2008

Dual roles of immunoregulatory cytokine TGF-beta in the pathogenesis of autoimmunity-mediated organ damage.

Vijay Saxena, Douglas W Lienesch, Min Zhou, Ramireddy Bommireddy, Mohamad Azhar, Thomas Doetschman, Ram Raj Singh

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

62 citing papers in PubMed, 113 citations in OpenAlex.

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  10. Influence ofInternational journal of molecular sciences · 2022
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2 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

Vijay SaxenaAutoimmunity and Tolerance Laboratory, Department of Medicine, University of California, Los Angeles 90095, USA.
Douglas W Lienesch
Min Zhou
Ramireddy Bommireddy
Mohamad Azhar
Thomas Doetschman
Ram Raj Singh
University of Cincinnati Medical Center · USImmune Tolerance Network · USUniversity of Cincinnati · US

Funding

Transforming Growth Factor beta in T-Cell Homeostasis and ToleranceR01AI067903 · NIAID · UNIVERSITY OF CINCINNATI · PI DOETSCHMAN, THOMAS · 2006 to 2010
$1.8M
TARGETED MUTATION OF TGF-BETA-1 IN ES CELLSR01HD026471 · NICHD · UNIVERSITY OF CINCINNATI · PI DOETSCHMAN, THOMAS · 1990 to 2005
$1.8M
Kidney Damage in Murine LupusR01AR050797 · NIAMS · UNIVERSITY OF CINCINNATI · PI SINGH, RAM RAJ · 2003 to 2006
$1.4M
Peptide Gene Vaccination in LupusR01AR047322 · NIAMS · UNIVERSITY OF CINCINNATI · PI SINGH, RAM RAJ · 2001 to 2005
$1.3M
Augementing Peptide-specific Tolerance in ImmuneNephrit*R21DK069282 · NIDDK · UNIVERSITY OF CINCINNATI · PI SINGH, RAM RAJ · 2004 to 2005
$462k
NIAID NIH HHS R01 AI067903NIAMS NIH HHS AR050797NIAMS NIH HHS AR47322NIAMS NIH HHS R01 AR047322NIAMS NIH HHS R01 AR050797NICHD NIH HHS R01 HD026471NIDDK NIH HHS DK69282NIDDK NIH HHS R21 DK069282
6 · The paper itself

Abstract

Ample evidence suggests a role of TGF-beta in preventing autoimmunity. Multiorgan inflammatory disease, spontaneous activation of self-reactive T cells, and autoantibody production are hallmarks of autoimmune diseases, such as lupus. These features are reminiscent of the immunopathology manifest in TGF-beta1-deficient mice. In this study, we show that lupus-prone (New Zealand Black and White)F(1) mice have reduced expression of TGF-beta1 in lymphoid tissues, and TGF-beta1 or TGF-beta1-producing T cells suppress autoantibody production. In contrast, the expression of TGF-beta1 protein and mRNA and TGF-beta signaling proteins (TGF-beta receptor type II and phosphorylated SMAD3) increases in the target organs, i.e., kidneys, of these mice as they age and develop progressive organ damage. In fact, the levels of TGF-beta1 in kidney tissue and urine correlate with the extent of chronic lesions that represent local tissue fibrosis. In vivo TGF-beta blockade by treatment of these mice with an anti-TGF-beta Ab selectively inhibits chronic fibrotic lesions without affecting autoantibody production and the inflammatory component of tissue injury. Thus, TGF-beta plays a dual, seemingly paradoxical, role in the development of organ damage in multiorgan autoimmune diseases. According to our working model, reduced TGF-beta in immune cells predisposes to immune dysregulation and autoantibody production, which causes tissue inflammation that triggers the production of anti-inflammatory cytokines such as TGF-beta in target organs to counter inflammation. Enhanced TGF-beta in target organs, in turn, can lead to dysregulated tissue repair, progressive fibrogenesis, and eventual end-organ damage.

Indexed as

AnimalsAutoantibodiesAutoimmune DiseasesFibrosisKidneyLupus Erythematosus, SystemicLymphoid TissueMiceMice, Mutant StrainsSignal TransductionTransforming Growth Factor betaAutoantibodiesTransforming Growth Factor beta

Identifiers

PMID18209088
PMCPMC2291535
OpenAlexW1846501109

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.