Cross Talk between β Cells and Immune Cells: What We Know, What We Think We Know, and What We Should Learn.

Abstract

Type 1 diabetes (T1D) is a disease whose pathogenesis is driven by both immune dysregulation and β-cell dysfunction. While the specialized structure and function of β cells make them vulnerable to autoimmunity, several surface receptor/ligand pairs underlie the cross talk engaged with T lymphocytes and other immune subsets. The expression of these ligands on β cells is coordinately up-regulated by the exposure to interferons, notably the type I interferons that represent the signature cytokines since the early preclinical stages of T1D. Yet, their interaction with receptors expressed on T lymphocytes can favor either β-cell vulnerability or protection. Despite several knowledge gaps, this novel holistic view of autoimmunity that incorporates both immune and β-cell-derived pathogenic drivers is starting to translate into novel therapeutic strategies aimed at decreasing vulnerability and/or increasing these protective mechanisms. This review summarizes the current knowledge in this evolving field, the assumptions that are often taken for granted but lack formal evidence, and the blind spots in this landscape that may hide further therapeutic opportunities.