Evidence map›Paper›PMID 39704171›Full record

ArticleJCI insight2024

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

Fernando Alvarez, Nicole V Acuff, Glenn M La Muraglia, Nazila Sabri, Marcos E Milla, Jill M Mooney, Matthew F Mackey, Mark Peakman, Ciriaco A Piccirillo

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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.

Fernando AlvarezDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
Nicole V AcuffSynthorx, a Sanofi company, La Jolla, California, USA.
Glenn M La MuragliaSanofi, Cambridge, Massachusetts, USA.
Nazila SabriSynthorx, a Sanofi company, La Jolla, California, USA.
Marcos E MillaSynthorx, a Sanofi company, La Jolla, California, USA.
Jill M MooneySynthorx, a Sanofi company, La Jolla, California, USA.
Matthew F MackeySanofi, Cambridge, Massachusetts, USA.
Mark PeakmanSanofi, Cambridge, Massachusetts, USA.
Ciriaco A PiccirilloDepartment of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deficits in IL-2 signaling can precipitate autoimmunity by altering the function and survival of FoxP3+ regulatory T cells (Tregs) while high concentrations of IL-2 fuel inflammatory responses. Recently, we showed that the non-beta IL-2 SYNTHORIN molecule SAR444336 (SAR'336) can bypass the induction of autoimmune and inflammatory responses by increasing its reliance on IL-2 receptor α chain subunit (CD25) to provide a bona fide IL-2 signal selectively to Tregs, making it an attractive approach for the control of autoimmunity. In this report, we further demonstrate that SAR'336 can support non-beta IL-2 signaling in murine Tregs and limit NK and CD8+ T cells' proliferation and function. Using a murine model of spontaneous type 1 diabetes, we showed that the administration of SAR'336 slows the development of disease in mice by decreasing the degree of insulitis through the expansion of antigen-specific Tregs over Th1 cells in pancreatic islets. Specifically, SAR'336 promoted the differentiation of IL-33-responsive (ST2+), IL-10-producing GATA3+ Tregs over other Treg subsets in the pancreas, demonstrating the ability of this molecule to further orchestrate Treg adaptation. These results offer insight into the capacity of SAR'336 to generate highly specialized, tissue-localized Tregs that promote restoration of homeostasis during ongoing autoimmune disease.

Indexed as

Diabetes Mellitus, Type 1Interleukin-2T-Lymphocytes, RegulatoryAnimalsAutoimmunityCD8-Positive T-LymphocytesDisease Models, AnimalFemaleInterleukin-10Interleukin-1 Receptor-Like 1 ProteinInterleukin-2 Receptor alpha SubunitInterleukin-33Islets of LangerhansMiceMice, Inbred NODRecombinant ProteinsaldesleukinIl1rl1 protein, mouseIl2ra protein, mouseIl33 protein, mouseInterleukin-10Interleukin-1 Receptor-Like 1 ProteinInterleukin-2Interleukin-2 Receptor alpha SubunitInterleukin-33Recombinant ProteinsAutoimmune diseasesAutoimmunityCytokinesT cellsTherapeutics

Identifiers

PMID39704171
PMCPMC11665582

What Socratic holds

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LicenceCC BY
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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 Socratic graph.