Journal article

Tolerance to Proinsulin-1 Reduces Autoimmune Diabetes in NOD Mice

Gaurang Jhala, Claudia Selck, Jonathan Chee, Chun-Ting J Kwong, Evan G Pappas, Helen E Thomas, Thomas WH Kay, Balasubramanian Krishnamurthy

FRONTIERS IN IMMUNOLOGY | FRONTIERS MEDIA SA | Published : 2021

Abstract

T-cell responses to insulin and its precursor proinsulin are central to islet autoimmunity in humans and non-obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes. Mice have two proinsulin genes proinsulin -1 and 2 that are differentially expressed, with predominant proinsulin-2 expression in the thymus and proinsulin-1 in islet beta-cells. In contrast to proinsulin-2, proinsulin-1 knockout NOD mice are protected from autoimmune diabetes. This indicates that proinsulin-1 epitopes in beta-cells maybe preferentially targeted by autoreactive T cells. To study the contribution of proinsulin-1 reactive T cells in autoimmune diabetes, we generated transgenic NOD mice with tetrac..

View full abstract

Grants

Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

This work was funded by the National Health and Medical Research Council of Australia (GNT1037321 and GNT1150425) and fellowship from Juvenile Diabetes Research Foundation (BK). The St Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria.