Association of Regulatory T-Cell Expansion With Progression of Amyotrophic Lateral Sclerosis A Study of Humans and a Transgenic Mouse Model

Rebecca K Sheean; Fiona C McKay; Erika Cretney; Christopher R Bye; Nirma D Perera; Doris Tomas; Richard A Weston; Karlene J Scheller; Elvan Djouma; Parvathi Menon; Stephen D Schibeci; Najwa Marmash; Justin J Yerbury; Stephen L Nutt; David R Booth; Graeme J Stewart; Mathew C Kiernan; Steve Vucic; Bradley J Turner

Journal article

Association of Regulatory T-Cell Expansion With Progression of Amyotrophic Lateral Sclerosis A Study of Humans and a Transgenic Mouse Model

Rebecca K Sheean, Fiona C McKay, Erika Cretney, Christopher R Bye, Nirma D Perera, Doris Tomas, Richard A Weston, Karlene J Scheller, Elvan Djouma, Parvathi Menon, Stephen D Schibeci, Najwa Marmash, Justin J Yerbury, Stephen L Nutt, David R Booth, Graeme J Stewart, Mathew C Kiernan, Steve Vucic, Bradley J Turner

JAMA NEUROLOGY | AMER MEDICAL ASSOC | Published : 2018

DOI: 10.1001/jamaneurol.2018.0035

Abstract

Importance: Neuroinflammation appears to be a key modulator of disease progression in amyotrophic lateral sclerosis (ALS) and thereby a promising therapeutic target. The CD4+Foxp3+ regulatory T-cells (Tregs) infiltrating into the central nervous system suppress neuroinflammation and promote the activation of neuroprotective microglia in mouse models of ALS. To our knowledge, the therapeutic association of host Treg expansion with ALS progression has not been studied in vivo. Objective: To assess the role of Tregs in regulating the pathophysiology of ALS in humans and the therapeutic outcome of increasing Treg activity in a mouse model of the disease. Design, Setting, and Participants: This p..

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University of Melbourne Researchers

Chris Bye Author Florey Department of Neuroscience and Mental Health

Stephen Nutt Author Medical Biology (w.e.h.i.)

Nirma Perera Author Florey Department of Neuroscience and Mental Health

Bradley Turner Author Florey Department of Neuroscience and Mental Health

Erika Cretney Author The Sir Peter Maccallum Department of Oncology

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Grants

Awarded by Australian National Health and Medical Research Council

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

Funding/Support: This article was supported by grants from the Australian National Health and Medical Research Council (grants 1104295 and 1104299, Dr Turner; grant 1047313, Dr Cretney), Stafford Fox Medical Research Foundation, MND Research Institute of Australia, Vowell Foundation, and Margaret Dawn Marks Charitable Trust Fund. Additional funding came from Forefront, a collaborative research group supported from the National Health and Medical Research Council of Australia (grant 1037746, Dr Kiernan). Drs Sheean, Bye, Weston, Scheller, and Turner and Ms Tomas, via their affiliation with the Florey Institute of Neuroscience and Mental Health, and Drs McKay, Booth, Stewart, and Vucic, and Mr Schibeci, via their affiliation with theWalter and Elisa Hall Institute, are supported by the Victorian Government and the Operational Infrastructure Support Grant. Dr Perera is supported by an Australian Postgraduate Award Scholarship.