Network approach reveals preferential T-cell and macrophage association with α-linked β-cells in early stage of insulitis in NOD mice.

Autor:	Balasenthilkumaran NV; Department of Bioengineering, Jacobs School of Engineering, University of California San Diego, San Diego, CA, United States., Whitesell JC; Department of Immunology and Microbiology, School of Medicine, Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Pyle L; Department of Pediatrics, University of Colorado School of Medicine, Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, United States., Friedman RS; Department of Immunology and Microbiology, School of Medicine, Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, United States., Kravets V; Department of Bioengineering, Jacobs School of Engineering, University of California San Diego, San Diego, CA, United States.; Department of Pediatrics, School of Medicine, University of California San Diego, San Diego, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in network physiology [Front Netw Physiol] 2024 Jun 24; Vol. 4, pp. 1393397. Date of Electronic Publication: 2024 Jun 24 (Print Publication: 2024).
DOI:	10.3389/fnetp.2024.1393397
Abstrakt:	One of the challenges in studying islet inflammation-insulitis-is that it is a transient phenomenon. Traditional reporting of the insulitis progression is based on cumulative, donor-averaged values of leucocyte density in the vicinity of pancreatic islets, that hinder intra- and inter-islet heterogeneity of disease progression. Here, we aimed to understand why insulitis is non-uniform, often with peri-insulitis lesions formed on one side of an islet. To achieve this, we demonstrated the applicability of network theory in detangling intra-islet multi-cellular interactions during insulitis. Specifically, we asked the question "What is unique about regions of the islet that interact with immune cells first". This study utilized the non-obese diabetic mouse model of type one diabetes and examined the interplay among α-, β-, T-cells, myeloid cells, and macrophages in pancreatic islets during the progression of insulitis. Disease evolution was tracked based on the T/β cell ratio in individual islets. In the early stage, we found that immune cells are preferentially interacting with α-cell-rich regions of an islet. At the islet periphery α-linked β-cells were found to be targeted significantly more compared to those without α-cell neighbors. Additionally, network analysis revealed increased T-myeloid, and T-macrophage interactions with all β-cells. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Balasenthilkumaran, Whitesell, Pyle, Friedman and Kravets.)
Databáze:	MEDLINE
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