Journal article

Cytotoxicity-Related Gene Expression and Chromatin Accessibility Define a Subset of CD4 T Cells That Mark Progression to Type 1 Diabetes

NG Bediaga, AL Garnham, G Naselli, E Bandala-Sanchez, NL Stone, J Cobb, JE Harbison, JM Wentworth, AG Ziegler, JJ Coupe, GK Smyth, LC Harrison

Diabetes | AMER DIABETES ASSOC | Published : 2022

Abstract

Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of children at risk associated with progression to islet autoimmunity. We analyzed gene expression with RNA sequencing in CD4+ and CD8+ T cells, natural killer (NK) cells, and B cells, and chromatin accessibility by assay for transposase- accessible chromatin sequencing (ATAC-seq) in CD4+ T cells, in five genetically at risk children with islet autoantibodies who progressed to diabetes over a ..

View full abstract

Grants

Awarded by Juvenile Diabetes Research Foundation Australia


Funding Acknowledgements

This research was supported by JDRF Australia (JDRFA)/National Health and Medical Research Council of Australia (NHMRC) Centre of Research Excellence for the Protection of Pancreatic Beta Cells (1078106), JDRFA Australian Type 1 Diabetes Clinical Research Network, JDRFA/The Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2019-899-M-N), and JDRF International (1-SRA-2018-543-S-B). Additional support was provided by an NHMRC Program Grant (LCH APP1150425) and NHMRC Research Fellowships (to G.K.S and L.C.H). The work was made possible through Victorian State Government Operational Infrastructure Support Program and NHMRC Research Institute Infrastructure Support Scheme.