Current Diabetes Reports

, 18:90 | Cite as

Immune Mechanisms and Pathways Targeted in Type 1 Diabetes

  • Laura M. Jacobsen
  • Brittney N. Newby
  • Daniel J. Perry
  • Amanda L. Posgai
  • Michael J. Haller
  • Todd M. BruskoEmail author
Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pathogenesis of Type 1 Diabetes


Purpose of Review

The immunosuppressive agent cyclosporine was first reported to lower daily insulin dose and improve glycemic control in patients with new-onset type 1 diabetes (T1D) in 1984. While renal toxicity limited cyclosporine’s extended use, this observation ignited collaborative efforts to identify immunotherapeutic agents capable of safely preserving β cells in patients with or at risk for T1D.

Recent Findings

Advances in T1D prediction and early diagnosis, together with expanded knowledge of the disease mechanisms, have facilitated trials targeting specific immune cell subsets, autoantigens, and pathways. In addition, clinical responder and non-responder subsets have been defined through the use of metabolic and immunological readouts.


Herein, we review emerging T1D biomarkers within the context of recent and ongoing T1D immunotherapy trials. We also discuss responder/non-responder analyses in an effort to identify therapeutic mechanisms, define actionable pathways, and guide subject selection, drug dosing, and tailored combination drug therapy for future T1D trials.


Immune therapy Clinical trial Type 1 diabetes Prevention Treatment Autoimmunity 



Type 1 diabetes


Network for Pancreatic Organ donors with Diabetes




First-degree relatives


Human leukocyte antigen


Odds ratios


T cell receptor


Insulin autoantibody


GAD65 autoantibody


Genome wide association study


Genetic risk score




Insulinoma-associated protein 2 autoantibody


Zinc transporter 8 autoantibody




Cell-free DNA


Effector T cell




Defective ribosomal products


Hybrid insulin peptides


Next-generation sequencing


Adaptive immune receptor repertoire


Regulatory T cells


Generally regarded as safe


Gut-associated lymphoid tissue


Anti-thymocyte globulin


Alum GAD bound to an aluminum hydroxide adjuvant


Mechanisms of action


Adoptive cell therapies


Graft-versus-host disease


Mesenchymal stem cells


Embryonic stem cells


Induced pluripotent stem cells


Umbilical cord blood


Chimeric antigen receptor


Chronic myelogenous leukemia


Inflammatory bowel disease


Juvenile idiopathic arthritis


Rheumatoid arthritis



The authors would like to thank Dr. Mark A. Atkinson for his comments and critical review of the manuscript.

Author Contributions

LMJ, BNN, DJP, ALP, and MJH wrote the manuscript; TMB conceived of and wrote the manuscript.


This effort was supported by grants from the NIH (P01 AI42288 and R01 DK106191 to TMB; F30 DK105788 to BNN), the JDRF (post-doctoral fellowships to LMJ (3-PDF-2018-579-A-N) and DJP (2-PDF-2016-207-A-N)), the Leona M. and Harry B. Helmsley Charitable Trust, and the McJunkin Family Charitable Foundation.

Compliance with Ethical Standards

Conflict of Interest

Laura M. Jacobsen, Brittney N. Newby, Daniel J. Perry, Amanda L. Posgai, Michael J. Haller, and Todd M. Brusko declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Laura M. Jacobsen
    • 1
  • Brittney N. Newby
    • 2
  • Daniel J. Perry
    • 2
  • Amanda L. Posgai
    • 2
  • Michael J. Haller
    • 1
  • Todd M. Brusko
    • 2
    Email author
  1. 1.Department of Pediatrics, College of MedicineUniversity of Florida Diabetes InstituteGainesvilleUSA
  2. 2.Department of Pathology, Immunology and Laboratory Medicine, College of MedicineUniversity of Florida Diabetes InstituteGainesvilleUSA

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