Peter J. Darlington

article

Helper CD4 T cells expressing granzyme B cause glial fibrillary acidic protein fragmentation in astrocytes in an MHCII‐independent manner

Brandon Stopnicki, Manon Blain, Qiao‐Ling Cui, Timothy E. Kennedy, more

Glia > 67 > 4 > 582 - 593

During inflammatory processes of the central nervous system, helper T cells have the capacity to cross the blood–brain barrier and injure or kill neural cells through cytotoxic mechanisms. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is part of the astrocyte cytoskeleton that can become fragmented in neuroinflammatory conditions. The mechanism of action by which...

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Reciprocal modulation of helper Th1 and Th17 cells by the β2‐adrenergic receptor agonist drug terbutaline

Catalina M. Carvajal Gonczi, Mahdieh Tabatabaei Shafiei, Ashley East, Erika Martire, more

The FEBS Journal > 284 > 18 > 3018 - 3028

Catecholamine hormones are powerful regulators of the immune system produced by the sympathetic nervous system (SNS). They regulate the adaptive immune system by altering T‐cell differentiation into T helper (Th) 1 and Th2 cell subsets, but the effect on Th17 cells is not known. Th17 cells, defined, in part, by chemokine receptor CCR6 and cytokine interleukin (IL)‐17A, are crucial for mediating certain...

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Comparative morphology and phagocytic capacity of primary human adult microglia with time-lapse imaging

Natalie Levtova, Luke M. Healy, Catalina Marysol Carvajal Gonczi, Brandon Stopnicki, more

Journal of Neuroimmunology > 2017 > 310 > C > 143-149

Microglia provide immune surveillance within the brain and spinal cord. Various microglial morphologies include ramified, amoeboid, and pseudopodic. The link between form and function is not clear, especially for human adult microglia which are limited in availability for study. Here, we examined primary human microglia isolated from normal-appearing white matter. Pseudopodic and amoeboid microglia...

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Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation

Peter J. Darlington, Tarik Touil, Jean‐Sebastien Doucet, Denis Gaucher, more

Annals of Neurology > 73 > 3 > 341 - 354

ObjectiveTo define changes in phenotype and functional responses of reconstituting T cells in patients with aggressive multiple sclerosis (MS) treated with ablative chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). MethodsClinical and brain magnetic resonance imaging measures of disease activity were monitored serially in patients participating in the Canadian MS HSCT Study...

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Neurite outgrowth is differentially impacted by distinct immune cell subsets

Madeline Pool, Isabel Rambaldi, Peter J. Darlington, Melissa C. Wright, more

Molecular and Cellular Neuroscience > 2012 > 49 > 1 > 68-76

Axonal damage can occur in the central nervous system following trauma, during the course of autoimmune and neurodegenerative disease and during viral and bacterial infections. The degree of axonal damage and absence of spontaneous repair are major determinants of long-term clinical outcome. While inflammation is a common feature of these conditions, the impact of particular immune cell subsets and...

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Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis

Peter J. Darlington, Marie‐Noëlle Boivin, Christel Renoux, Moïra François, more

Annals of Neurology > 68 > 4 > 540 - 545

Human mesenchymal stem cells (hMSCs) are being considered for clinical trials of multiple sclerosis (MS). We examined the effects of adult bone marrow‐derived hMSCs on responses of primary human Th1, Th17, and Th1/17 double‐expressing T‐cell subsets, all implicated in MS. As expected, soluble products from hMSCs inhibited Th1 responses; however, Th17 responses were increased. Secretion of interleukin...

article

Fingolimod (FTY720) Enhances Remyelination Following Demyelination of Organotypic Cerebellar Slices

Veronique E. Miron, Samuel K. Ludwin, Peter J. Darlington, Andrew A. Jarjour, more

The American Journal of Pathology > 2010 > 176 > 6 > 2682-2694

Remyelination, which occurs subsequent to demyelination, contributes to functional recovery and is mediated by oligodendrocyte progenitor cells (OPCs) that have differentiated into myelinating cells. Therapeutics that impact remyelination in the CNS could be critical determinants of long-term functional outcome in multiple sclerosis (MS). Fingolimod is a S1P receptor modulator in MS clinical trials...

article

Abnormal B‐cell cytokine responses a trigger of T‐cell–mediated disease in MS?

Amit Bar‐Or, Lama Fawaz, Boli Fan, Peter J. Darlington, more

Annals of Neurology > 67 > 4 > 452 - 461

ObjectiveTo study antibody‐independent contributions of B cells to inflammatory disease activity, and the immune consequences of B‐cell depletion with rituximab, in patients with multiple sclerosis (MS). MethodsB‐Cell effector‐cytokine responses were compared between MS patients and matched controls using a 3‐signal model of activation. The effects of B‐cell depletion on Th1/Th17 CD4 and CD8 T‐cell...

INFONA - science communication portal

Search results for: Peter J. Darlington

Helper CD4 T cells expressing granzyme B cause glial fibrillary acidic protein fragmentation in astrocytes in an MHCII‐independent manner

Reciprocal modulation of helper Th1 and Th17 cells by the β2‐adrenergic receptor agonist drug terbutaline

Comparative morphology and phagocytic capacity of primary human adult microglia with time-lapse imaging

Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation

Neurite outgrowth is differentially impacted by distinct immune cell subsets

Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis

Fingolimod (FTY720) Enhances Remyelination Following Demyelination of Organotypic Cerebellar Slices

Abnormal B‐cell cytokine responses a trigger of T‐cell–mediated disease in MS?

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