Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes

Torabi Baghkomeh, Forough, Vadakekolathu, Jayakumar, Wyatt, Rebecca , Leete, Pia, Tombs, Melissa A., Richardson, Carolyn C., Boocock, David J., Turner, Mark D., Morgan, Noel G., Richardson, Sarah J. and Christie, Michael R. (2023) Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes. Diabetic Medicine, 40 (9). ISSN 1464-5491

Full content URL: https://doi.org/10.1111/dme.15155

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Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes

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Abstract

Aims
Morphological studies of pancreas samples obtained from young people with recent-onset type 1 diabetes have revealed distinct patterns of immune cell infiltration of the pancreatic islets suggestive of two age-associated type 1 diabetes endotypes that differ by inflammatory responses and rates of disease progression. The objective of this study was to investigate whether these proposed disease endotypes are associated with pathological differences in immune cell activation and cytokine secretion by applying multiplexed gene expression analysis to pancreatic tissue from recent-onset type 1 diabetes cases.

Methods
RNA was extracted from samples of fixed, paraffin-embedded pancreas tissue from type 1 diabetes cases characterised by endotype, and from controls without diabetes. Expression levels of 750 genes associated with autoimmune inflammation were determined by hybridisation to a panel of capture and reporter probes and these were counted as a measure of gene expression. Normalised counts were analysed for differences in expression between 29 type 1 diabetes cases and 7 controls without diabetes, and between the two type 1 diabetes endotypes.

Results
Ten inflammation-associated genes, including INS, were significantly under-expressed in both endotypes and 48 genes were more highly expressed. A different set of 13 genes associated with development, activation and migration of lymphocytes was uniquely over-expressed in the pancreas of people developing diabetes at younger age.

Conclusions
The results provide evidence that histologically-defined type 1 diabetes endotypes differ in their immunopathology and identify inflammatory pathways specifically involved in disease developing at a young age, essential for a better understanding of disease heterogeneity.

Keywords:Chemokines, Inflammation, B-Lymphocytes, T-Lymphocytes, type 1 diabetes
Subjects:C Biological Sciences > C760 Biomolecular Science
A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B131 Cellular Pathology
Divisions:COLLEGE OF HEALTH AND SCIENCE > School of Life and Environmental Sciences > Department of Life Sciences
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ID Code:54924
Deposited On:09 Jun 2023 15:02

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