The Role of β Cell Stress and Neo-Epitopes in the Immunopathology of Type 1 Diabetes

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2021 Mar 8

PMID 33679609

Citations 19

Authors

Jon D Piganelli

Mark J Mamula

Eddie A James

Affiliations

Soon will be listed here.

Abstract

Due to their secretory function, β cells are predisposed to higher levels of endoplasmic reticulum (ER) stress and greater sensitivity to inflammation than other cell types. These stresses elicit changes in β cells that alter their function and immunogenicity, including defective ribosomal initiation, post-translational modifications (PTMs) of endogenous β cell proteins, and alternative splicing. Multiple published reports confirm the presence of not only CD8+ T cells, but also autoreactive CD4+ T cells within pancreatic islets. Although the specificities of T cells that infiltrate human islets are incompletely characterized, they have been confirmed to include neo-epitopes that are formed through stress-related enzymatic modifications of β cell proteins. This article summarizes emerging knowledge about stress-induced changes in β cells and data supporting a role for neo-antigen formation and cross-talk between immune cells and β cells that provokes autoimmune attack - leading to a breakdown in tissue-specific tolerance in subjects who develop type 1 diabetes.

Citing Articles

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