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Title: | Interleukin-26, preferentially produced by TH17 lymphocytes, regulates CNS barrier function | Authors: | BROUX, Bieke Zandee, Stephanie Gowing, Elizabeth Charabati, Marc Lecuyer, Marc-Andre Tastet, Olivier Hachehouche, Lamia Bourbonniere, Lyne Ouimet, Jean-Philippe Lemaitre, Florent Larouche, Sandra Cayrol, Romain Bouthillier, Alain Moumdjian, Robert Lahav, Boaz Poirier, Josee Duquette, Pierre Arbour, Nathalie PEELEN, Evelyn Prat, Alexandre |
Issue Date: | 2020 | Publisher: | LIPPINCOTT WILLIAMS & WILKINS | Source: | Neurology-Neuroimmunology & Neuroinflammation, 7 (6) (Art N° e870) | Abstract: | Objective To investigate the involvement of interleukin (IL)-26 in neuroinflammatory processes in multiple sclerosis (MS), in particular in blood-brain barrier (BBB) integrity. Methods Expression of IL-26 was measured in serum, CSF, in vitro differentiated T helper (T-H) cell subsets, and postmortem brain tissue of patients with MS and controls by ELISA, quantitative PCR, and immunohistochemistry. Primary human and mouse BBB endothelial cells (ECs) were treated with IL-26 in vitro and assessed for BBB integrity. RNA sequencing was performed on IL-26-treated human BBB ECs. Myelin oligodendrocyte glycoprotein(35-55) experimental autoimmune encephalomyelitis (EAE) mice were injected IP with IL-26. BBB leakage and immune cell infiltration were assessed in the CNS of these mice using immunohistochemistry and flow cytometry. Results IL-26 expression was induced in T-H lymphocytes by T(H)17-inducing cytokines and was upregulated in the blood and CSF of patients with MS. CD4(+)IL-26(+) T lymphocytes were found in perivascular infiltrates in MS brain lesions, and both receptor chains for IL-26 (IL-10R2 and IL-20R1) were detected on BBB ECs in vitro and in situ. In contrast to IL-17 and IL-22, IL-26 promoted integrity and reduced permeability of BBB ECs in vitro and in vivo. In EAE, IL-26 reduced disease severity and proinflammatory lymphocyte infiltration into the CNS, while increasing infiltration of Tregs. Conclusions Our study demonstrates that although IL-26 is preferentially expressed by T(H)17 lymphocytes, it promotes BBB integrity in vitro and in vivo and is protective in chronic EAE, highlighting the functional diversity of cytokines produced by T(H)17 lymphocytes. | Notes: | Prat, A (corresponding author), Univ Montreal, Fac Med, Multiple Sclerosis Clin, Res Ctr,Ctr Hosp Univ Montreal CRCHUM,Dept Neuros, Montreal, PQ, Canada. a.prat@umontreal.ca |
Other: | Prat, A (corresponding author), Univ Montreal, Fac Med, Multiple Sclerosis Clin, Res Ctr,Ctr Hosp Univ Montreal CRCHUM,Dept Neuros, Montreal, PQ, Canada. a.prat@umontreal.ca | Document URI: | http://hdl.handle.net/1942/33833 | ISSN: | 2332-7812 | e-ISSN: | 2332-7812 | DOI: | 10.1212/NXI.0000000000000870 | ISI #: | WOS:000618947900004 | Rights: | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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e870.full.pdf | Published version | 1.51 MB | Adobe PDF | View/Open |
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