Universität zu Köln

Sona, Chandan ORCID: 0000-0003-3107-016X, Yeh, Yu-Te, Patsalos, Andreas ORCID: 0000-0002-9022-4985, Halasz, Laszlo ORCID: 0000-0003-4726-7012, Yan, Xin, Kononenko, Natalia L., Nagy, Laszlo ORCID: 0000-0001-6653-2155 and Poy, Matthew N. ORCID: 0000-0002-4904-2426 (2022). Evidence of islet CADM1-mediated immune cell interactions during human type 1 diabetes. JCI Insight, 7 (6). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

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Abstract

BACKGROUND. Pathophysiology of type 1 diabetes (T1D) is illustrated by pancreatic islet infiltration of inflammatory lymphocytes, including CD8(+) T cells; however, the molecular factors mediating their recruitment remain unknown. We hypothesized that single-cell RNA-sequencing (scRNA-Seq) analysis of immune cell populations isolated from islets of NOD mice captured gene expression dynamics providing critical insight into autoimmune diabetes pathogenesis. METHODS. Pancreatic sections from human donors were investigated, including individuals with T1D, autoantibody-positive (aAb(+)) individuals, and individuals without diabetes who served as controls. IHC was performed to assess islet hormones and both novel and canonical immune cell markers that were identified from unbiased, state-of-the-art workflows after reanalyzing murine scRNA-Seq data sets. RESULTS. Computational workflows identified cell adhesion molecule 1-mediated (Cadm1-mediated) homotypic binding among the most important intercellular interactions among all cell clusters, as well as Cadm1 enrichment in macrophages and DCs from pancreata of NOD mice. Immunostaining of human pancreata revealed an increased number of CADM1(+)glucagon(+) cells adjacent to CD8(+) T cells in sections from T1D and aAb(+) donors compared with individuals without diabetes. Numbers of CADM1(+)CD68(+) peri-islet myeloid cells adjacent to CD8(+) T cells were also increased in pancreatic sections from both T1D and aAb(+) donors compared with individuals without diabetes. CONCLUSION. Increased detection of CADM1(+) cells adjacent to CD8(+) T cells in pancreatic sections of individuals with T1D and those who were aAb(+) validated workflows and indicated CADM1-mediated intercellular contact may facilitate islet infiltration of cytotoxic T lymphocytes and serve as a potential therapeutic target for preventing T1D pathogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sona, Chandan UNSPECIFIED orcid.org/0000-0003-3107-016X UNSPECIFIED Yeh, Yu-Te UNSPECIFIED UNSPECIFIED UNSPECIFIED Patsalos, Andreas UNSPECIFIED orcid.org/0000-0002-9022-4985 UNSPECIFIED Halasz, Laszlo UNSPECIFIED orcid.org/0000-0003-4726-7012 UNSPECIFIED Yan, Xin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kononenko, Natalia L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nagy, Laszlo UNSPECIFIED orcid.org/0000-0001-6653-2155 UNSPECIFIED Poy, Matthew N. UNSPECIFIED orcid.org/0000-0002-4904-2426 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-679141
DOI:	10.1172/jci.insight.153136
Journal or Publication Title:	JCI Insight
Volume:	7
Number:	6
Date:	2022
Publisher:	AMER SOC CLINICAL INVESTIGATION INC
Place of Publication:	ANN ARBOR
ISSN:	2379-3708
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language T-CELLS; ADHESION MOLECULE; MASS; IDENTIFICATION; HOMEOSTASIS; PROGRESSION; INSULITIS; PEPTIDES; RECEPTOR; EPITOPE Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67914