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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<...

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:Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis.
Authors:Darlington PJ,  Stopnicki B,  Touil T,  Doucet JS,  Fawaz L,  Roberts ME,  Boivin MN,  Arbour N,  Freedman MS,  Atkins HL,  Bar-Or A
Link:https://www.ncbi.nlm.nih.gov/pubmed/29867923?dopt=Abstract
Category:Front Immunol
PMID:29867923
Dept Affiliation: PERFORM
1 Departments of Exercise Science and Biology, PERFORM Centre, Concordia University, Montreal, QC, Canada.
2 Neuroimmunology Unit, McGill University and Montreal Neurological Institute, Montreal, QC, Canada.
3 Clinical Biological Imaging and Genetic Repository, McGill University, Montreal, QC, Canada.
4 Department of Neurosciences, Université de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
5 Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
6 Blood and Marrow Transplant Program, Ottawa General Hospital, Ottawa, ON, Canada.
7 Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Description:

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

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

Abstract

In autoimmunity, the balance of different helper T (Th) cell subsets can influence the tissue damage caused by autoreactive T cells. Pro-inflammatory Th1 and Th17 T cells are implicated as mediators of several human autoimmune conditions such as multiple sclerosis (MS). Autologous hematopoietic stem cell transplantation (aHSCT) has been tested in phase 2 clinical trials for MS patients with aggressive disease. Abrogation of new clinical relapses and brain lesions can be seen after ablative aHSCT, accompanied by significant reductions in Th17, but not Th1, cell populations and activity. The cause of this selective decrease in Th17?cell responses following ablative aHSCT is not completely understood. We identified an increase in the kinetics of natural killer (NK) cell reconstitution, relative to CD4+ T cells, in MS patients post-aHSCT, resulting in an increased NK cell:CD4+ T cell ratio that correlated with the degree of decrease in Th17 responses. Ex vivo removal of NK cells from post-aHSCT peripheral blood mononuclear cells resulted in higher Th17?cell responses, indicating that NK cells can regulate Th17 activity. NK cells were also found to be cytotoxic to memory Th17?cells, and this toxicity is mediated through NKG2D-dependent necrosis. Surprisingly, NK cells induced memory T cells to secrete more IL-17A. This was preceded by an early rise in T cell expression of RORC and IL17A mRNA, and could be blocked with neutralizing antibodies against CD58, a costimulatory receptor expressed on NK cells. Thus, NK cells provide initial co-stimulation that supports the induction of a Th17 response, followed by NKG2D-dependent cytotoxicity that limits these cells. Together these data suggest that rapid reconstitution of NK cells following aHSCT contribute to the suppression of the re-emergence of Th17?cells. This highlights the importance of NK cells in shaping the reconstituting immune system following aHSCT in MS patients.

PMID: 29867923 [PubMed - in process]