Our understanding of the interactions between immune cells and beta cells in the pancreas: autoimmune mechanisms leading to type 1 diabetes.

Abstract

Introduction: Type 1 diabetes (T1D) has long been viewed as an immune-driven disease characterized by the destruction of otherwise healthy pancreatic beta cells. However, growing evidence indicates that beta cells may actively contribute to disease initiation. Intrinsic dysfunction - such as impaired protein processing, endoplasmic reticulum stress, neoantigen formation, and early upregulation of major histocompatibility complex (MHC) class I - could increase beta-cell immunogenicity and promote autoimmune recognition. This emerging paradigm has significant implications for prevention and therapeutic strategies.

Areas covered: This review synthesizes experimental, translational, and clinical evidence supporting beta cell stress and dysfunction as central components of T1D pathogenesis. It examines intrinsic beta cell pathways, mechanisms of immune recognition, and therapeutic approaches aimed at preserving beta-cell integrity. These findings challenge the traditional immune-centric model and support a more integrated view of disease progression, emphasizing the interplay between beta cell vulnerability and immune activation.

Expert opinion: Effective prevention will likely require combination strategies that address both beta cell stress and autoimmunity. Approaches integrating beta cell protective agents with antigen-specific tolerance therapies may delay or prevent progression when applied early. Stage-adapted interventions targeting both beta cell resilience and immune modulation may redefine T1D prevention and improve management of pre-symptomatic individuals.