Targeting the GM-CSF receptor for the treatment of CNS autoimmunity.

Autor: Ifergan I; Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States., Davidson TS; Department of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Granta Park, Great Abington, CB21 6GH, UK., Kebir H; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Département de Neurosciences, Faculté de Médecine, Université de Montréal, Montréal, QC H2X 0A9, Canada., Xu D; Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States., Palacios-Macapagal D; Department of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Granta Park, Great Abington, CB21 6GH, UK., Cann J; Department of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Granta Park, Great Abington, CB21 6GH, UK., Rodgers JM; Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States., Hunter ZN; Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States., Pittet CL; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Département de Neurosciences, Faculté de Médecine, Université de Montréal, Montréal, QC H2X 0A9, Canada., Beddow S; Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States., Jones CA; Department of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Granta Park, Great Abington, CB21 6GH, UK., Prat A; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Département de Neurosciences, Faculté de Médecine, Université de Montréal, Montréal, QC H2X 0A9, Canada., Sleeman MA; Department of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd, Granta Park, Great Abington, CB21 6GH, UK. Electronic address: sleemanm@medimmune.com., Miller SD; Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States. Electronic address: s-d-miller@northwestern.edu.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2017 Nov; Vol. 84, pp. 1-11. Date of Electronic Publication: 2017 Jun 20.
DOI: 10.1016/j.jaut.2017.06.005
Abstrakt: In multiple sclerosis (MS), there is a growing interest in inhibiting the pro-inflammatory effects of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to evaluate the therapeutic potential and underlying mechanisms of GM-CSF receptor alpha (Rα) blockade in animal models of MS. We show that GM-CSF signaling inhibition at peak of chronic experimental autoimmune encephalomyelitis (EAE) results in amelioration of disease progression. Similarly, GM-CSF Rα blockade in relapsing-remitting (RR)-EAE model prevented disease relapses and inhibited T cell responses specific for both the inducing and spread myelin peptides, while reducing activation of mDCs and inflammatory monocytes. In situ immunostaining of lesions from human secondary progressive MS (SPMS), but not primary progressive MS patients shows extensive recruitment of GM-CSF Rα + myeloid cells. Collectively, this study reveals a pivotal role of GM-CSF in disease relapses and the benefit of GM-CSF Rα blockade as a potential novel therapeutic approach for treatment of RRMS and SPMS.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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