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Human Mesenchymal Stem Cells Impact Th17 and Th1 Responses Through a Prostaglandin E2 and Myeloid-Dependent Mechanism.

Author(s): Rozenberg A, Rezk A, Boivin MN, Darlington PJ, Nyirenda M, Li R, Jalili F, Winer R, Artsy EA, Uccelli A, Reese JS, Planchon SM, Cohen JA, Bar-Or A

Stem Cells Transl Med. 2016 Nov;5(11):1506-1514 Authors: Rozenberg A, Rezk A, Boivin MN, Darlington PJ, Nyirenda M, Li R, Jalili F, Winer R, Artsy EA, Uccelli A, Reese JS, Planchon SM, Cohen JA, Bar-Or A

Article GUID: 27400792
Comparative morphology and phagocytic capacity of primary human adult microglia with time-lapse imaging.

Author(s): Levtova N, Healy LM, Gonczi CMC, Stopnicki B, Blain M, Kennedy TE, Moore CS, Antel JP, Darlington PJ

J Neuroimmunol. 2017 09 15;310:143-149 Authors: Levtova N, Healy LM, Gonczi CMC, Stopnicki B, Blain M, Kennedy TE, Moore CS, Antel JP, Darlington PJ

Article GUID: 28606377
Detecting glycogen in peripheral blood mononuclear cells with periodic acid schiff staining.

Author(s): Tabatabaei Shafiei M, Carvajal Gonczi CM, Rahman MS, East A, François J, Darlington PJ

Detecting glycogen in peripheral blood mononuclear cells with periodic acid schiff staining.
J Vis Exp. 2014 Dec 23;(94):
Authors: Tabatabaei Shafiei M, Carvajal Gonczi CM, Rahman MS, East A, François J, Darlington PJ
Abstract
Periodic acid ...

Article GUID: 25548935
Reciprocal modulation of helper Th1 and Th17 cells by the β2-adrenergic receptor agonist drug terbutaline.

Author(s): Carvajal Gonczi CM, Tabatabaei Shafiei M, East A, Martire E, Maurice-Ventouris MHI, Darlington PJ

FEBS J. 2017 09;284(18):3018-3028 Authors: Carvajal Gonczi CM, Tabatabaei Shafiei M, East A, Martire E, Maurice-Ventouris MHI, Darlington PJ

Article GUID: 28710773
Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis.

Author(s): Darlington PJ, Stopnicki B, Touil T, Doucet JS, Fawaz L, Roberts ME, Boivin MN, Arbour N, Freedman MS, Atkins HL, Bar-Or A

Front Immunol. 2018;9:834 Authors: Darlington PJ, Stopnicki B, Touil T, Doucet JS, Fawaz L, Roberts ME, Boivin MN, Arbour N, Freedman MS, Atkins HL, Bar-Or A

Article GUID: 29867923
Helper CD4 T cells expressing granzyme B cause glial fibrillary acidic protein fragmentation in astrocytes in an MHCII-independent manner.

Author(s): Stopnicki B, Blain M, Cui QL, Kennedy TE, Antel JP, Healy LM, Darlington PJ

Glia. 2019 04;67(4):582-593 Authors: Stopnicki B, Blain M, Cui QL, Kennedy TE, Antel JP, Healy LM, Darlington PJ

Article GUID: 30444064
Title:Helper CD4 T cells expressing granzyme B cause glial fibrillary acidic protein fragmentation in astrocytes in an MHCII-independent manner.
Authors:Stopnicki B,  Blain M,  Cui QL,  Kennedy TE,  Antel JP,  Healy LM,  Darlington PJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/30444064?dopt=Abstract
DOI:10.1002/glia.23503
Category:Glia
PMID:30444064
Dept Affiliation: PERFORM
1 Department of Exercise Science, Department of Biology, PERFORM Centre, Concordia University, Montréal, Quebec, Canada.
2 Department of Neurology and Neurosurgery, Montreal Neurological Institute, and McGill University, Montreal, Quebec, Canada.
3 Neuroimmunology Unit, McGill University, Montréal, Quebec, Canada.

Description:

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

Glia. 2019 04;67(4):582-593

Authors: Stopnicki B, Blain M, Cui QL, Kennedy TE, Antel JP, Healy LM, Darlington PJ

Abstract

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 helper T cells with cytotoxic properties injure astrocytes is not completely understood. Primary human astrocytes were obtained from fetal brain tissue. Human helper (CD4+ ) T cells were isolated from peripheral blood mononuclear cells and activated with the superantigen staphylococcal enterotoxin E (SEE). Granzyme B was detected by enzyme linked immunosorbent assay and intracellular flow cytometry. GFAP fragmentation was monitored by western blotting. Cell death was monitored by lactic acid dehydrogenase release and terminal biotin-dUTP nick labeling (TUNEL). Astrocyte migration was monitored by scratch assay. Adult human oligodendrocytes were cultured with sublethally injured astrocytes to determine support function. Helper T cells activated with SEE expressed granzyme B but not perforin. Helper T cells released granzyme B upon contact with astrocytes and caused GFAP fragmentation in a caspase-dependent, MHCII-independent manner. Sublethally injured astrocytes were not apoptotic; however, their processes were thin and elongated, their migration was attenuated, and their ability to support oligodendrocytes was reduced in vitro. Helper T cells can release granzyme B causing sublethal injury to astrocytes, which compromises the supportive functions of astrocytes. Blocking these pathways may lead to improved resolution of neuroinflammatory lesions.

PMID: 30444064 [PubMed - in process]