Beta cell and immune cell interactions in autoimmune type 1 diabetes: How they meet and talk to each other

Abstract

Background: The highly complex pathogenesis of Type 1 Diabetes is driven by several immune cell types with both effector and regulatory characteristics, which ultimately ends in the destruction of the insulin-producing beta cells. There are multiple layers of interaction between these immune cell populations and the pancreatic islets.

Scope of review: In this review article, we aim to discuss important recent insights into the multiple layers of interaction between immune cell populations and the pancreatic islets. Specifically, we discuss the environment where immune and beta cell interactions occur, the key cell types and molecules involved, and the outcomes of these interactions.

Major conclusions: Most of the molecular mechanisms underlying aberrant immune cell activation and impaired immune tolerance remain insufficiently understood, which hinders the development of efficient prevention and treatment strategies. In order to overcome this knowledge gap, a better understanding of the complex interactions of immune cells and beta cells, including both the underlying protective and pathogenic mechanisms is urgently required.

Keywords: Autoimmune diabetes; Autoimmunity; Beta cells; Immune Regulation; Immune cells; Type 1 diabetes.

Graphical abstract

Figure 1

Role of classical and non-classical HLA-I expression in beta cell – immune cell interactions in T1D. High expression of HLA-I can have both protective and detrimental effects. In T1D hyperexpression of classical and non-classical HLA class I in beta cells is thought to be critical in early disease progression, facilitating the effective engagement of autoreactive CD8⁺ cytotoxic T cells, which recognize specific islet autoantigens. (created with BioRender).

Figure 2

Cellular and molecular mechanisms contributing to the prevention or development of T1D. Beta cell antigens are released by damaged beta cells. These antigens are processed by pancreas-resident antigen-presenting cells (APC). Following activation APCs migrate to the pancreatic lymph nodes where they prime pathogenic beta cell antigen-specific T cells. On the other hand, tolerogenic APCs can prime and expand Tregs which can directly suppress autoreactive T cells, including but not limited to the release of IL10 and TGFβ. Beta cell killing in the pancreas happens by autoreactive T cells, NK cells and macrophages, besides other through the release of cytokines such as IL1β, IFNγ and TNF. Furthermore, dendritic cells (DC) release IL12 to sustain effector functions of activated T cells and NK cells. Lastly, changes in the islet microenvironment as well as the release of chemokines by beta cells can recruit additional lymphocytes and macrophages, further driving the autoimmune process. (created with BioRender).