The Chicken or the Egg Dilemma: Understanding the Interplay between the Immune System and the β Cell in Type 1 Diabetes.
Maria Skjøtt HansenPravil PokharelJon PiganelliLori SusselPublished in: Cold Spring Harbor perspectives in medicine (2024)
In this review, we explore the complex interplay between the immune system and pancreatic β cells in the context of type 1 diabetes (T1D). While T1D is predominantly considered a T-cell-mediated autoimmune disease, the inability of human leukocyte antigen (HLA)-risk alleles alone to explain disease development suggests a role for β cells in initiating and/or propagating disease. This review delves into the vulnerability of β cells, emphasizing their susceptibility to endoplasmic reticulum (ER) stress and protein modifications, which may give rise to neoantigens. Additionally, we discuss the role of viral infections as contributors to T1D onset, and of genetic factors with dual impacts on the immune system and β cells. A greater understanding of the interplay between environmental triggers, autoimmunity, and the β cell will not only lead to insight as to why the islet β cells are specifically targeted by the immune system in T1D but may also reveal potential novel therapeutic interventions.
Keyphrases
- induced apoptosis
- type diabetes
- cell cycle arrest
- cardiovascular disease
- single cell
- gene expression
- stem cells
- endoplasmic reticulum
- endothelial cells
- physical activity
- genome wide
- oxidative stress
- cell therapy
- drug delivery
- risk assessment
- glycemic control
- climate change
- skeletal muscle
- dna methylation
- cancer therapy
- peripheral blood
- copy number