Journal article

Soluble FAS ligand is not required for pancreatic islet inflammation or beta-cell destruction in non-obese diabetic mice

Prerak M Trivedi, Stacey Fynch, Lucy M Kennedy, Jonathan Chee, Balasubramanian Krishnamurthy, Lorraine A O'Reilly, Andreas Strasser, Thomas WH Kay, Helen E Thomas

Cell Death Discovery | NATURE PUBLISHING GROUP | Published : 2019

Abstract

CD8+ T cells play a central role in beta-cell destruction in type 1 diabetes. CD8+ T cells use two main effector pathways to kill target cells, perforin plus granzymes and FAS ligand (FASL). We and others have established that in non-obese diabetic (NOD) mice, perforin is the dominant effector molecule by which autoreactive CD8+ T cells kill beta cells. However, blocking FASL pharmacologically was shown to protect NOD mice from diabetes, indicating that FASL may have some role. FASL can engage with its receptor FAS on target cells either as membrane bound or soluble FASL. It has been shown that membrane-bound FASL is required to stimulate FAS-induced apoptosis in target cells, whereas excess..

View full abstract

Grants

Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

We thank S. Litwak, L. Elkerbout, T. Kay, E. Wilson and V. Moshovakis for technical assistance and animal husbandry. This work was funded by a National Health and Medical Research Council of Australia program grant (APP1037321 to H.E.T. and T.W.K. and APP1131233 to A.S.) and fellowship (APP1042735 to H.E.T. and APP1020363 to A.S.). The work was supported by the Operational Infrastructure Support Scheme of the Government of Victoria.