Evidence map›Paper›PMID 41959203›Full record

ArticlebioRxiv : the preprint server for biology2026

Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes.

Jyotirmoy Roy, Yifei Jiang, Runbo Mao, Jessica L King, Amod Talekar, Lillian Holman, Haoxuan Zeng, Xin Luo, Peter Sajjakulnukit, Brianna Ha and 12 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Jyotirmoy RoyDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Yifei JiangDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Runbo MaoGilbert S. Omenn Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, USA.
Jessica L KingDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Amod TalekarDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Lillian HolmanDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Haoxuan ZengGilbert S. Omenn Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, USA.
Xin LuoGilbert S. Omenn Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, USA.
Peter SajjakulnukitDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, USA.
Brianna HaDepartment of Chemical Engineering, University of Michigan, Ann Arbor, USA.
Kai LiuGilbert S. Omenn Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, USA.
Elizabeth J BealerDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Laila M RadDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Shahzad SohailDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Antonio HolmesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Bryan WonskiDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Kathryn KangDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Dominik AwadDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, USA.
Aaron H MorrisDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.
Costas A LyssiotisDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, USA.ORCID 0000-0001-9309-6141
Jie LiuGilbert S. Omenn Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, USA.
Lonnie D SheaDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, USA.

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Eric R. Fearon · 1988 to 2026
$178.2M
RESEARCH TRAINING IN EXPERIMENTAL IMMUNOPATHOLOGYT32AI007413 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Bethany B. Moore · 1993 to 2026
$9.8M
Tissue engineering tools for monitoring the cellular and molecular response to therapyR01CA272940 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JACQUELINE SARA JERUSS, Lonnie D Shea · 2023 to 2026
$1.7M
Scaffolds for culture and transplantation of islet organoidsR01DK121462 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHEA, LONNIE D, SPENCE, JASON · 2020 to 2022
$1.7M
CTSA Postdoctoral T32 at the University of MichiganT32TR004764 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VICKI L ELLINGROD, Steven Edward Harte · 2024 to 2026
$1.4M
MICHR-Translational Science Immersion (MICHR-TSI)R25TR004776 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI VICKI L ELLINGROD, Susan Woolford · 2024 to 2026
$324k
NCATS NIH HHS R25 TR004776NCATS NIH HHS T32 TR004764NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA272940NIAID NIH HHS T32 AI007413NIDDK NIH HHS R01 DK121462
6 · The paper itself

Abstract

In Type 1 Diabetes (T1D), disease onset and response to immunotherapy vary widely among individuals, reflecting heterogeneous stage-specific immune dysregulation that remains undefined. To investigate this heterogeneity, we engineered a microporous polycaprolactone scaffold that forms a synthetic immunological niche (IN) upon subcutaneous implantation, enabling in vivo capture of systemic immune dysregulation. In non-obese diabetic (NOD) mice, longitudinal transcriptomic profiling of IN-infiltrating cells identified early-stage genes relatively enriched for myeloid cells, followed by progressive increases in T cell-associated dysregulation at later stages that distinguished T1D progressors from non-progressors. We derived an early-stage IN-based T1D gene signature capturing immune alterations. The signature stratified NOD progressors from non-progressors as early as 6 weeks of age and was conserved across human T1D datasets, distinguishing T1D from non-diabetic individuals in spleen and pancreatic lymph node samples, but not peripheral blood. Signature-based stratification further revealed enrichment of macrophage-associated TNF-α pathways in NOD progressors, validated in human T1D islets. Given heterogeneous response to anti-TNF-α therapy, IN profiling identified resistance-associated mechanisms and enabled derivation of a pathway score that prospectively distinguished treatment-sensitive from resistant mice prior to therapy, establishing the IN as a minimally invasive platform for detecting stage-wise immune dysregulation and stratifying immunotherapy response in T1D.

Identifiers

PMID41959203
PMCPMC13060903

What OpenQuestion holds

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Registered trials

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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.