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New Insights into the Pathogenesis of Type 1 Diabetes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 November 2025) | Viewed by 1592

Special Issue Editor


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Guest Editor
Infectivology and Clinical Trials Research Department, Children’s Hospital Bambino Gesù, Viale San Paolo 15, 00146 Rome, Italy
Interests: autoimmunity; type 1 diabetes; endocrinopathies; T regulatory cells; autoreactive T cells; nanotechnologies; NK cells; extracellular vesicles; immunoregulation
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Special Issue Information

Dear Colleagues,

Insulin-dependent diabetes mellitus (type 1 diabetes, T1D) is a multifactorial autoimmune disease with a strong genetic component. The disorder occurs in individuals genetically predisposed to human leukocyte antigen (HLA) as a consequence of organ-specific immune destruction of the insulin-producing cells in the islets of Langerhans within the pancreas. As a genetic background, dominant loci within the major histocompatibility complex (MHC) and the HLA region predisposing to the disease were recognized in both the NOD and human disease.

The pathogenesis of this multifactorial disorder requires the contribution of genetics, still-unknown environmental factors, and stochastic events. It is generally recognized that T1D derives from a breakdown in immune regulation that leads to the expansion of autoreactive CD4+ and CD8+ T cells, autoantibody-producing B lymphocytes, and activation of the innate immune system.

In this Special Issue, we discuss recent discoveries on the pathogenesis of T1D that constitute the background for the development of novel immunotherapies.

Dr. Alessandra Fierabracci
Guest Editor

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Keywords

  • type 1 diabetes
  • insulin-dependent diabetes mellitus
  • human leukocyte antigen (HLA)
  • pathogenesis

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Published Papers (1 paper)

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Research

11 pages, 558 KB  
Article
Preclinical Assessment in Transgenic NOD Mice of a Novel Immunotherapy for Type 1 Diabetes: Lipoplexes Down-Modulate the Murine C1858T Ptpn22 Variant In Vitro
by Irene Mezzani, Antonella Accardo, Emanuele Bellacchio, Luca Fais, Carlo Diaferia and Alessandra Fierabracci
Int. J. Mol. Sci. 2025, 26(23), 11241; https://doi.org/10.3390/ijms262311241 - 21 Nov 2025
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Abstract
The C1858T PTPN22 (R620W) variant has been implicated in the pathogenesis of several autoimmune disorders and represents a promising immunotherapeutic target for Type 1 diabetes. We have been implementing a novel immunotherapeutic approach based on the use of lipoplexes that deliver siRNA duplexes. [...] Read more.
The C1858T PTPN22 (R620W) variant has been implicated in the pathogenesis of several autoimmune disorders and represents a promising immunotherapeutic target for Type 1 diabetes. We have been implementing a novel immunotherapeutic approach based on the use of lipoplexes that deliver siRNA duplexes. The efficacy and safety of lipoplexes was previously demonstrated in vitro in halting variant expression in the peripheral blood of patients. Preclinical safety and efficacy must be ascertained in vivo in appropriate animal models before clinical investigations can be undertaken, according to regulatory authorities in Europe. In the light of the foregoing, this study aims to verify that lipoplexes against the murine Ptpn22-R619W, equivalent to the human PTPN22-R620W, could be used for animal experimentation. The murine fibroblast cell line L929 was transfected with the PF62-pLentiPtpn22-R619W plasmid. We designed specific siRNA duplexes for the Ptpn22-R619W allele and formulated them into cationic lipoplexes in order to halt variant expression in the transfected L929 cell line. Transfection of fibroblasts expressing R619W using lipoplexes resulted in efficient silencing at 100 pmol siRNA after 48 h post-transfection, reaching higher significant knockdown after 72 h. Lipoplexes efficiently suppress pathogenic Ptpn22 variant expression in vitro, supporting the feasibility of a pre-clinical platform for testing of in vivo lipoplexes in CRISPR-engineered NOD/ShiLtJ mice carrying the R619W mutation. Full article
(This article belongs to the Special Issue New Insights into the Pathogenesis of Type 1 Diabetes)
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