Evidence map›Paper›PMID 36221192›Full record

ArticleBiotechnology and bioengineering2023

Nanoparticle dose and antigen loading attenuate antigen-specific T-cell responses.

Liam M Casey, Joseph T Decker, Joseph R Podojil, Laila Rad, Kevin R Hughes, Justin A Rose, Ryan M Pearson, Stephen D Miller, Lonnie D Shea

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

12 citing papers in PubMed, 12 citations in OpenAlex.

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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

9 authors at 3 institutions in 1 country.

Liam M CaseyDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Joseph T DeckerDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.ORCID 0000-0001-7914-4741
Joseph R PodojilDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, llinois, USA.
Laila RadDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Kevin R HughesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Justin A RoseDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Ryan M PearsonDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
Stephen D MillerDepartment of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, llinois, USA.
Lonnie D SheaDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.ORCID 0000-0002-9296-9673
University of Michigan · USNorthwestern University · USUniversity of Maryland, Baltimore · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
STATISTICAL MODEL OF THE AIDS EPIDEMICR01AI028076 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI PAGANO, MARCELLO · 1989 to 2004
$1.8M
Chimeric Antigen Receptor T Cell Design Through Living Cell Systems BiologyK01EB028877 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DECKER, JOSEPH THOMAS · 2019 to 2022
$492k
NCI NIH HHS P30 CA046592NIAID NIH HHS R01 AI028076NIBIB NIH HHS K01 EB028877NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

Immune-mediated hypersensitivities such as autoimmunity, allergy, and allogeneic graft rejection are treated with therapeutics that suppress the immune system, and the lack of specificity is associated with significant side effects. The delivery of disease-relevant antigens (Ags) by carrier systems such as poly(lactide-co-glycolide) nanoparticles (PLG-Ag) and carbodiimide (ECDI)-fixed splenocytes (SP-Ag) has demonstrated Ag-specific tolerance induction in model systems of these diseases. Despite therapeutic outcomes by both platforms, tolerance is conferred with different efficacy. This investigation evaluated Ag loading and total particle dose of PLG-Ag on Ag presentation in a coculture system of dendritic cells (DCs) and Ag-restricted T cells, with SP-Ag employed as a control. CD25 expression was observed in nearly all T cells even at low concentrations of PLG-Ag, indicating efficient presentation of Ag by dendritic cells. However, the secretion of IL-2, Th1, and Th2 cytokines (IFNγ and IL-4, respectively) varied depending on PLG-Ag concentration and Ag loading. Concentration escalation of soluble Ag resulted in an increase in IL-2 and IFNγ and a decrease in IL-4. Treatment with PLG-Ag followed a similar trend but with lower levels of IL-2 and IFNγ secreted. Transcriptional Activity CEll ARrays (TRACER) were employed to measure the real-time transcription factor (TF) activity in Ag-presenting DCs. The kinetics and magnitude of TF activity was dependent on the Ag delivery method, concentration, and Ag loading. Ag positively regulated IRF1 activity and, as carriers, NPs and ECDI-treated SP negatively regulated this signaling. The effect of Ag loading and dose on tolerance induction were corroborated in vivo using the delayed-type hypersensitivity (DTH) and experimental autoimmune encephalomyelitis (EAE) mouse models where a threshold of 8 μg/mg Ag loading and 0.5 mg PLG-Ag dose were required for tolerance. Together, the effect of Ag loading and dosing on in vitro and in vivo immune regulation provide useful insights for translating Ag-carrier systems for the clinical treatment of immune disorders.

Indexed as

Encephalomyelitis, Autoimmune, ExperimentalNanoparticlesAnimalsAntigensInterleukin-2Interleukin-4MiceT-LymphocytesAntigensInterleukin-2Interleukin-4autoimmunenanoparticlestolerance

Identifiers

PMID36221192
PMCPMC9999438
OpenAlexW4304607106

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.