title: IL-25 prevents T cell-mediated neurotoxicity by decreasing LFA-1 expression.
abstract: Autoimmune diseases such as multiple sclerosis (MS) are thought to develop due to a dysregulation in the normal T(H)1-T(H)17/T(H)2 immune system balance, where pro-inflammatory responses with a T(H)1/T(H)17 prevalence develop. Some therapeutic treatments in MS promote a shift toward a TH2-prevalent environment and this has been shown to be protective. However, not all patients respond to current immunomodulatory treatments in MS so that new immunomodulatory drugs that can promote a shift of the immune system into an anti-inflammatory T(H)2 status are needed. IL-25 is a cytokine of the IL-17 family with powerful anti-inflammatory properties. This study demonstrates that IL-25 exerts neuroprotective functions by reducing T cell-mediated killing of human fetal neurons. The mechanism of action of this IL-25-mediated neuroprotective effect appears to be linked to reduction in the expression of the adhesion molecule LFA-1, which is relevant in stabilizing the immune synapse during cytotoxicity.
authors.affiliation: Centre for Neuroscience, Department of Medicine, University of Alberta, Edmonton, Alberta T6G 3G3, Canada.
authors.forename: Diane A
authors.initials: DA
authors.lastname: Turner
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Haile
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giuliani
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005333:Fetus / Q000166:cytology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010047:Ovalbumin / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors
chemical_list: D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D017077:Culture Media, Conditioned; D016207:Cytokines; C486701:IL25 protein, human; D020381:Interleukin-17; D015851:Interleukin-7; D016169:Lymphocyte Function-Associated Antigen-1; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D010047:Ovalbumin
keywords: CD4(+); IL-25; LFA-1; Multiple sclerosis; Neuroprotection; T(H)2