Editorial: Immunopathology of Type 1 Diabetes

Le résumé fourni par la source

DiabetesOur understanding of the islet-immune interface in autoimmune diabetes has exploded with the vast array of knowledge coming from recent works.Historically we know that genetic susceptibility and environmental influences trigger, or perpetuate gradual autoimmune destruction and damage to the insulin-producing islet beta (b) cells.However, the events leading to the breakdown in tolerance towards islet b cells, and the ensuing pro-inflammatory cytokine laden environment that perpetuates T cell-mediated b cell destruction, remain elusive.This timely Research Topic comprises a compendium of 5 original research articles and 15 reviews focusing on recent advances in the immunology of type 1 diabetes (T1D) that build on earlier observations and provide new knowledge.These articles center on environmental drivers of b cell destruction and use new models and technologies to interrogate factors influencing the breakdown of self-tolerance, enhancing our understanding of T1D immunopathology.In a thorough review, Quinn et al. describe data from past and present clinical trials that have assessed environmental elements associated with progression to T1D.The authors examined the likelihood of true causality of many favored initiators (beyond the well-characterized genetic predisposition, primarily at the HLA loci) activating self-reactive T cells that target b cells, in this heterogeneous condition.Environmental determinants, including enterovirus infection, rapid weight gain in early life, and the microbiome, correlated highly with T1D incidence, suggesting a 'threshold hypothesis' where genetic and environmental factors interact to promote T1D over time.The pancreatropic viruses, particularly the T1D-associated coxsackievirus B (CVB), are prominent contenders.In support of the viral induction hypothesis, Morse and Horwitz provide a compelling review describing how the antiviral response can modulate the microbiome, causing dysbiosis, and diabetes onset.This work stresses the importance of communication between the intestinal microbiota and the local immune population in dictating the outcome of the interaction.This interaction is also influenced by other predisposing factors, such as genetic predisposition, viral responses leading to dysbiosis and the background state of the host immune system.Further, Lincez et al. used elegant animal models that express altered expression of two key viral sensors-melanoma differentiation-associated protein 5 (MDA5) and toll-like receptor-3 (TLR-3).They showed that alterations in sensing of the same virus (CVB) by MDA5 and TLR3 led to unique IFN-a and IFN-b

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