Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different approaches to explain the biology of T1D, beyond the presence and activity of autoreactive lymphocytes. In this review, we propose inflammatory pathways as triggers for T1D. Within the scope of those inflammatory pathways and in understanding the pathogenesis of disease, we suggest that viruses, in particular Coxsackieviruses, act by causing a type 1 interferonopathy within the pancreas and the microenvironment of the islet. As such, this connection and common thread represents an exciting platform for the development of new diagnostic, treatment and/or prevention options.

The first Fresh Ideas, Foundational Experiments (FIFE): Immunology and Diabetes symposia workshop took place in 2016 and exemplified the active interest of a number of several investigators interested the global rise in the incidence of type 1 diabetes (T1D). This increase does not correlate with genetic drift and indicates that environmental exposures are playing an increasingly significant role. Despite major biomedical and technological advances in diagnosis and treatment, treatments are frequently insufficient as they do not inhibit the progression of the underlying autoimmune response and often fail to prevent life-threatening complications. T1D is the result of autoimmune destruction of the insulin-producing beta cells of the pancreas, and the precise, mechanistic contribution of the immune system to disease pathogenesis and progression remains to be fully characterized. Ultimately, the combinatorial effect of concurrent factors, including beta cell fragility, exogenous stressors, and genetic priming of the innate and adaptive immune system, work together to induce T1D autoimmunity. Thus, T1D is the result of immunological defects and environmental pathogens, requiring the sustained attention of collaborative research teams such as FIFE: I & D with varied perspectives, unified by the universally held goal of finding a sustainable, life-long cure. Herein, the authors provide perspective on various fields in T1D research highlighted by speakers participating in the inaugural FIFE symposium.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system without a clear cause. Epstein-Barr virus (EBV) is proposed to contribute to the pathogenesis of MS through unknown mechanisms. Evidence for a role of EBV infection in MS comes from both epidemiological and experimental studies, however, due to its narrow host tropism, there are currently few suitable animal models of MS that incorporate EBV infection. Recent advancements in humanized mouse modelling has enabled direct infection for the study of EBV-associated malignancies. We therefore chose to evaluate the role of EBV infection in humanized mice with experimental autoimmune encephalomyelitis (EAE), a widely used model of MS. Immunocompromised mice were engrafted with peripheral blood mononuclear cells (PBMC) derived from individuals with relapsing MS (RRMS) or from matched healthy EBV seropositive or seronegative donors. We observed that HuPBMC mice induced with EAE developed ascending paralysis, weight loss and signs of discomfort consistent with classical EAE models. Further, HuPBMC EAE showed significant T cell infiltration of both the brain and spinal cord, notably of IFN gamma-expressing CD4 and CD8 T cells, resulting in spinal cord and cerebellar demyelination. HuPBMC EAE mice derived from EBV seropositive donors developed earlier disease onset with more severe clinical symptoms compared to EBV seronegative donor-derived mice. We also observed increase disease severity among mice derived from RRMS patients compared to healthy controls. With continued improvement and characterization of this novel humanized EAE model, additional environmental and genetic risk factors can be evaluated in a system with human immune-mediated pathology.