# Modulating immune response for the prevention and treatment of type 1 diabetes

**Authors:** Dilrasbonu Vohidova, Prasi Desai, Alvaro Moreno Lozano, Omid Veiseh

PMC · DOI: 10.3389/fimmu.2026.1715863 · Frontiers in Immunology · 2026-02-16

## TL;DR

This review discusses how immune modulation can prevent and treat type 1 diabetes by stopping autoimmune attacks and improving islet cell replacement.

## Contribution

The paper provides a comprehensive review of recent immunomodulation strategies for T1D prevention and islet cell replacement.

## Key findings

- FDA approval of the first T1D prevention drug shows promise for early intervention.
- Islet transplantation can achieve long-term insulin independence but requires lifelong immunosuppression.
- Advances in islet engineering and immunomodulatory biomaterials aim to reduce the need for immunosuppression.

## Abstract

In type 1 diabetes (T1D), chronic autoimmune responses lead to the destruction of β-cells in pancreatic islets. As more of the β-cell mass is destroyed, the disease progresses, resulting in insulin deficiency. Recent discoveries uncovering the mechanisms behind the autoimmune attack on β-cells have allowed for a better understanding of the development of the disease and categorizing it into stages of progression. Further, FDA approval of the first drug for the prevention of T1D demonstrated the potential for early intervention therapies. Meanwhile, for patients whose β-cell mass is fully destroyed, islet transplantation has been shown to achieve long-term insulin independence. However, this procedure requires lifelong immunosuppression, which can increase the risk of infections and malignancies. Here, we will review recent advances in immunomodulation approaches for the prevention of type 1 diabetes and strategies for islet cell replacement. First, we introduce the pathogenesis of T1D and the stages of the disease that require different immunomodulatory approaches. Then, we will discuss current immunotherapies for the prevention of T1D, highlighting strategies such as antigen-specific, immune blockade, and cell-based therapies, which aim to stop autoimmune attack for patients at early stages of T1D. Afterwards, we discuss advancement for islet replacement approaches, highlighting islet engineering, device encapsulation, and immunomodulatory biomaterials, which aim to prolong the survival of transplanted islets and minimize the need for immunosuppression. We expect this review to provide a comprehensive understanding of current advances in immunomodulatory therapies for T1D.

## Linked entities

- **Diseases:** type 1 diabetes (MONDO:0005147)

## Full-text entities

- **Genes:** ICOS (inducible T cell costimulator) [NCBI Gene 29851] {aka AILIM, CD278, CVID1}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, Nr1i3 (nuclear receptor subfamily 1, group I, member 3) [NCBI Gene 12355] {aka CAR, CAR-beta, Care2, ESTM32, MB67}, Hspa5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 14828] {aka Bip, D2Wsu141e, D2Wsu17e, Grp78, Hsce70, SEZ-7}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Cd28 (CD28 antigen) [NCBI Gene 12487], IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, PTPN22 (protein tyrosine phosphatase non-receptor type 22) [NCBI Gene 26191] {aka LYP, LYP1, LYP2, PEP, PTPN22.5, PTPN22.6}, G6pc2 (glucose-6-phosphatase, catalytic, 2) [NCBI Gene 14378] {aka G6pc-rs, IGRP}, Ccr4 (C-C motif chemokine receptor 4) [NCBI Gene 12773] {aka C-C CKR-4, CHEMR1, Cmkbr4, LESTR, Sdf1r}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, Il3 (interleukin 3) [NCBI Gene 16187] {aka BPA, Csfmu, HCGF, Il-3, MCGF, PSF}, CD40 [NCBI Gene 101085363], TNF-alpha [NCBI Gene 493755], H2-Ab1 (histocompatibility 2, class II antigen A, beta 1) [NCBI Gene 14961] {aka Abeta, H-2Ab, H2-Ab, I-Abeta, IAb, Ia-2}, Egr3 (early growth response 3) [NCBI Gene 13655] {aka EGR-3, Pilot}, IL-21 [NCBI Gene 101087399], CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, Cd47 (CD47 antigen (Rh-related antigen, integrin-associated signal transducer)) [NCBI Gene 16423] {aka 9130415E20Rik, B430305P08Rik, IAP, Itgp}, APC [NCBI Gene 101096138], CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Ciita (class II transactivator) [NCBI Gene 12265] {aka C2ta, EG669998, Gm9475, Mhc2ta}, B2m (beta-2 microglobulin) [NCBI Gene 12010] {aka Ly-m11, beta2-m, beta2m}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, CD40L [NCBI Gene 493850], SST (somatostatin) [NCBI Gene 6750] {aka SMST, SST1}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Fasl (Fas ligand) [NCBI Gene 14103] {aka APT1LG1, CD178, CD95-L, CD95L, Fas-L, Faslg}, Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, Pdcd1lg2 (programmed cell death 1 ligand 2) [NCBI Gene 58205] {aka B7-DC, Btdc, F730015O22Rik, PD-L2}, Lgals9 (lectin, galactose binding, soluble 9) [NCBI Gene 16859] {aka LGALS35, Lgals5, gal-9, galectin-9}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Cxcl12 (C-X-C motif chemokine ligand 12) [NCBI Gene 20315] {aka Pbsf, Scyb12, Sdf1, Tlsf, Tpar1}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, CD2 [NCBI Gene 493790], Chga (chromogranin A) [NCBI Gene 12652] {aka ChrA, cgA}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, Il21 (interleukin 21) [NCBI Gene 60505] {aka IL-21}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, CD58 [NCBI Gene 101085141], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, P4hb (prolyl 4-hydroxylase, beta polypeptide) [NCBI Gene 18453] {aka ERp59, PDI, Pdia1, Thbp}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}
- **Diseases:** T1D (MESH:D003922), beta-cell dysfunction (MESH:D007340), thromboembolic (MESH:D013923), kidney diseases (MESH:D007674), multiple sclerosis (MESH:D009103), stage 3 (MESH:D062706), thrombosis (MESH:D013927), rheumatoid arthritis (MESH:D001172), insulin deficiency (MESH:D007333), toxicity (MESH:D064420), infections (MESH:D007239), hypoglycemia (MESH:D007003), autoimmune (MESH:D001327), systemic lupus erythematosus (MESH:D008180), damage (MESH:D020263), celiac disease (MESH:D002446), hypoglycemic (MESH:C000721848), HIP (OMIM:142700), PD (MESH:D010300), fibrosis (MESH:D005355), inflammation (MESH:D007249), graft versus host disease (MESH:D006086), Sjogren's disease (MESH:D012859), cancer (MESH:D009369), NOD (MESH:D003920), alloimmune (MESH:C536394)
- **Chemicals:** aluminum hydroxide (MESH:D000536), carbon dioxide (MESH:D002245), triazole (MESH:D014230), poly(beta-amino ester)) (MESH:C507253), glucose (MESH:D005947), polyurethane (MESH:D011140), PEG-b-PPS (MESH:C515871), teplizumab (MESH:C502540), PLG (MESH:D011098), TMTD (MESH:D013893), PLGA (MESH:D000077182), CsA (MESH:D016572), SA (MESH:D000077145), tacrolimus (MESH:D016559), silicon (MESH:D012825), NHP (-), golimumab (MESH:C529000), HS100 (MESH:C027178), rituximab (MESH:D000069283), polyester (MESH:D011091), Dex (MESH:D003907), STZ (MESH:D013311), alum (MESH:C041524), water (MESH:D014867), sulfobetaine (MESH:C483727), blood glucose (MESH:D001786), Siplizumab (MESH:C544394), Ustekinumab (MESH:D000069549), lithium peroxide (MESH:C000721051), tocilizumab (MESH:C502936), PTFE (MESH:D011138), oxygen (MESH:D010100), Zn (MESH:D015032), alginate (MESH:D000464), ladarixin (MESH:C511776), vitamin D (MESH:D014807), gold (MESH:D006046), MMF (MESH:D009173), polymer (MESH:D011108), RAPA- (MESH:D020123), PEG (MESH:D011092)
- **Species:** Macaca mulatta (rhesus macaque, species) [taxon 9544], Cercopithecidae (monkey, family) [taxon 9527], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** rs3087243, rs231775
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), Balb/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

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## References

272 references — full list in the complete paper: https://tomesphere.com/paper/PMC12950593/full.md

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Source: https://tomesphere.com/paper/PMC12950593