< Back to previous page

Project

Neutrophils: neglected as potential players in autoimmune type 1 diabetes initiation, progression, and perpetuation

While the role of innate immune cells such macrophages and dendritic cells in the initiation and perpetuation of autoimmune type 1 diabetes (T1D) have been well documented, the particular actions of neutrophils remain unfairly overlooked in the etiology of this chronic disease. As neutrophils can influence cells of the innate and adaptive immune system, a better characterization of the neutrophil population during disease development is needed, and could provide novel insights into whether neutrophils have divergent developmental branches or different maturation sequences influenced by tissue environmental cues. Here, we aim to identify distinct neutrophil populations during T1D development in the non-obese diabetic (NOD) mouse model using state-of-the-art technologies (i.e., multiparameter flow cytometry, single-cell CITE-sequencing, and spatial transcriptomics) and exploit perceptions, obtained via data integration, in the design of neutrophil-related immunotherapeutics to delay or prevent T1D onset. As emerging data indicate that neutrophil extracellular traps are implicated in T1D development, we aim to study the therapeutic potential of small-molecule isozyme-specific PAD4 and TGM2 inhibitors, which catalyze protein modifications known to be involved in certain types of autoimmunity, in delaying or preventing T1D onset in mice. If this strategy proves successful, these PAD4 and TGM2 blockers could be powerful therapies in human individuals at-risk of developing T1D.

Date:1 Jan 2023 →  Today
Keywords:type 1 diabetes, neutrophils, prevention, single-cell omics, translational
Disciplines:Applied immunology, Autoimmunity, Endocrinology, Metabolic diseases