Diabetes type 1 is an autoimmune disease where macrophages in the pancreas destroy the beta cells in the islets of Langerhans. As a result, frequent injections of insulin are required by the patient to maintain glucose homeostasis. The pathogenic mechanism behind the development of diabetes type 1 is still elusive. Studying the differentiation pathway of the macrophages that ultimately destroy beta cells will help us to better understand these mechanisms. In vitro, monocytes can be induced into either M1 or M2 types of macrophages, where each type expresses distinct biomarker. However, macrophages that exist in vivo are not necessarily sorted into either slot, rather these phenotypes may exhibit hybrid behavior. We set out to phenotype and characterize macrophages to study whether there are proteomic differences between macrophages inside the islets of Langerhans compared to other parts of the pancreas in rodent genetic models of diabetes type I. We have used the bottom-up proteomic approach with data-independent acquisition mass spectrometry to study macrophages that have been differentiated in vitro into M1 and M2 cells. Analysis with data-independent acquisition allows us to achieve greater detail of the proteome while it is a more robust method for quantitation compared to traditional data-dependent acquisition. Preliminary data indicate that the two phenotypes M1 and M2 have &gt;100 proteins that are differentially expressed. Now we are collecting cells from specific parts of the pancreas using magnetic-activated cell sorting to conduct a biological study of a genetically modified strain of mice that exhibit diabetes type 1. This will provide information whether these macrophages differentiate into different phenotypes, and how close to the two extremes M1 and M2 they are. In turn, unraveling the location-specific proteome and phenotypes of various macrophages in the pancreas will provide a better understanding of the pathogenesis for diabetes type 1.

Phenotyping macrophages involved in the onset of diabetes type 1 with label-free and quantitative proteomics

2019 Fall National Meeting

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