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

Torabi, F, Vadakekolathu, J ORCID: https://orcid.org/0000-0002-2671-4285, Wyatt, R, Leete, P, Tombs, MA, Richardson, CC, Boocock, DJ ORCID: https://orcid.org/0000-0002-7333-3549, Turner, MD ORCID: https://orcid.org/0000-0001-7175-1053, Morgan, NG, Richardson, SJ and Christie, MR, 2023. Differential expression of genes controlling lymphocyte differentiation and migration in two distinct endotypes of type 1 diabetes. Diabetic Medicine. ISSN 0742-3071

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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.

Item Type:	Journal article
Alternative Title:	Pancreatic gene expression in endotypes of type 1 diabetes [running title]
Publication Title:	Diabetic Medicine
Creators:	Torabi, F., Vadakekolathu, J., Wyatt, R., Leete, P., Tombs, M.A., Richardson, C.C., Boocock, D.J., Turner, M.D., Morgan, N.G., Richardson, S.J. and Christie, M.R.
Publisher:	Wiley
Date:	29 May 2023
ISSN:	0742-3071
Identifiers:	Number Type 10.1111/dme.15155 DOI 1769365 Other
Rights:	Copyright © 2023 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	08 Jun 2023 15:10
Last Modified:	08 Jun 2023 15:10
URI:	https://irep.ntu.ac.uk/id/eprint/49147

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