Title: Granzyme A Deficiency Breaks Immune Tolerance and Promotes Autoimmune Diabetes Through a Type I Interferon-Dependent Pathway
Authors: Mollah, ZUA
Quah, HS
Graham, KL
Jhala, G
Krishnamurthy, B
Dharma, JFM
Chee, J
Trivedi, PM
Pappas, EG
Mackin, L
Chu, EPF
Akazawa, S
Fynch, S
Hodson, C
Deans, AJ
Trapani, JA
Chong, MMW
Bird, PI
Brodnicki, TC
Thomas, HE
Kay, TWH
Issue Year: 2017
Series Diabetes:
Abstract Granzyme A is a protease implicated in the degradation of intracellular DNA. Nucleotide complexes are known triggers of systemic autoimmunity, but a role in organ-specific autoimmune disease has not been demonstrated. To investigate whether such a mechanism could be an endogenous trigger for autoimmunity, we examined the impact of granzyme A deficiency in the NOD mouse model of autoimmune diabetes. Granzyme A deficiency resulted in an increased incidence in diabetes associated with accumulation of ssDNA in immune cells and induction of an interferon response in pancreatic islets. Central tolerance to proinsulin in transgenic NOD mice was broken on a granzyme A-deficient background. We have identified a novel endogenous trigger for autoimmune diabetes and an in vivo role for granzyme A in maintaining immune tolerance.
URI: https://publications.svi.edu.au/publications/4787
Other Identifiers 10.2337/db17-0517
Publication type Article