Editorial : Immunological and virological aspects of the pathogenesis of type 1 diabetes

Didier HOBER^*

• Other

Lalani et al used an immortalized trophoblast cells infected with CVB4 for identifying microRNAs. A novel microRNA has the potential to be an early biomarker of CVB4-induced type 1 diabetes. The inhibition of this microRNA can reduce the replication of the virus suggesting that targeting microRNAs may be relevant approach to fight CVB-induced T1DM ( A novel microRNA promotes coxsackievirus B4 infection of pancreatic β cells. doi: 10.3389/fimmu.2024.1414894).A non-synonymous single-nucleotide polymorphisms (SNP) associated with T1D is in the interferon-induced helicase C domain-containing protein 1 (IFIH1), which encodes an anti-viral cytosolic RNA sensor. Substitution of one amino acid (IFIH1A946T) confers an increased risk for T1D. In IFIH1A946T risk variant (IFIH1 R ) knock-in mice on the non-obese diabetic (NOD) mouse background, Stock et al observed a significant acceleration of diabetes onset in (IFIH1 R ) females compared to non-risk (IFIH1 NR ) mice. In (IFIH1 R ) mice the frequency and activation of immune cells were altered. The data indicate that IFIH1 R may contribute to T1D pathogenesis (The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner. doi: 10.3389/fimmu.2024.1349601).T1DM has a significant impact on the whole life of diabetic patients due to T1DM-related complications especially macrovascular complications. There is a heterogeneity in type 1 diabetes mellitus (T1D) and therefore the risk of complications varies markedly between patients. In the paper entitled Blood immune cell profiling in adults with longstanding type 1 diabetes is associated with macrovascular complications (doi: 10.3389/fimmu.2024.1401542) , He et al have studied the blood immune cell profile of adult patients with longstanding T1DM and healthy controls by FACS analysis followed by a machine-learning based elastic-net classification model. This study shows that there are two distinct immunological profiles in adults with longstanding type 1 diabetes; one group of patients has a stronger pro-inflammatory profile and is associated with a higher rate of diabetes-related macrovascular complications.The survival and function of islet allografts and the prevention of T1DM are two major concerns. These issues have been addressed in murine models of transplantation and in NOD mice by Chuang et al (Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models. doi: 10.3389/fimmu.2024.1484425). This team develops small-molecule inhibitors (SMIs) of the CD40-CD40L(CD154) costimulatory protein-protein interaction, and in this paper the effect of two such SMIS: DRI-C21041 and DRI-C21095. This study shows that SMIs can inhibit the TNF superfamily protein-protein interaction and that these molecules through CD40-CD40L blockade can be useful in islet transplantation and T1D prevention.T1DM can be an adverse reaction to immunotherapy. A patient developed T1DM following treatment with Envafolimab, a PD-L1 immune checkpoint inhibitor. TADM was induced by the immunemodulating effects of Envafolimab and was not due to a pre-existing autoimmune condition because diabetes-related autoantibodies were absent in this patient. This case report draws attention to the fact that studies are needed to elucidate the mechanisms of the diabetogenic effect of immunotherapy to better understand the pathogenesis of T1DM (Li et al. Case report: A case of type 1 diabetes with diabetic ketoacidosis induced by envafolimab treatment in hepatocellular carcinoma. doi: 10.3389/fimmu.2025.1505195).The collection of articles at Frontiers in Immunology dedicated to the immunological and virological aspects of the pathogenesis of T1DM highlights that the research is active to better understand the pathogenesis of this autoimmune disease and to develop strategies to improve the management of patients.