Neurol Neuroimmunol Neuroinflamm 2020 11 11;7(6). Epub 2020 Aug 11.
From the Neuroimmunology Unit and Multiple Sclerosis Clinic (B.B., S.Z., E.G., M.C., M.-A.L., O.T., L.H., L.B., J.-P.O., F.L., S.L., R.C., B.L., J.P., P.D., N.A., E.P., A.P.), The Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Department of Neuroscience, Faculty of Medicine, Université de Montréal, Canada; Hasselt University (B.B.), Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; and Division of Neurosurgery (A.B., R.M.), Centre Hospitalier de l'Université de Montréal (CHUM), Faculty of Medicine, Université de Montréal, Canada.
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) 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 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 lymphocytes by T17-inducing cytokines and was upregulated in the blood and CSF of patients with MS. CD4IL-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 T17 lymphocytes, it promotes BBB integrity in vitro and in vivo and is protective in chronic EAE, highlighting the functional diversity of cytokines produced by T17 lymphocytes.