Blood brain barrier inhibitor

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Interleukin-26, preferentially produced by TH17 lymphocytes, regulates CNS barrier function.Broux B, Zandee S, Gowing E, Charabati M, Lécuyer MA, Tastet O, Hachehouche L, Bourbonnière L, Ouimet JP, Lemaitre F, Larouche S, Cayrol R, Bouthillier A, Moumdjian R, Lahav B, Poirier J, Duquette P, Arbour N, Peelen E, Prat A.Neurol Neuroimmunol Neuroinflamm. 2020 Aug 11;7(6):e870. doi: 10.1212/NXI.0000000000000870. Print 2020 Nov.PMID: 32788322

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 (TH) 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 glycoprotein35-55 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 TH lymphocytes by TH17-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 TH17 lymphocytes, it promotes BBB integrity in vitro and in vivo and is protective in chronic EAE, highlighting the functional diversity of cytokines produced by TH17 lymphocytes.

Interleukin 26 (IL-26), is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death. IL-26, a human TH17 cell–derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, TH17 cell–derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The IL-26–DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor

IL-26 is a 171-amino acid protein, which is similar in amino acid sequence to interleukin 10. It was originally called AK155 and signals through a receptor complex comprising two distinct proteins called IL-20 receptor 1 and IL-10 receptor 2. By signaling through this receptor complex, IL-26 induces rapid phosphorylation of the transcription factors STAT1 and STAT3, which enhance IL-10 and IL-8 secretion and as expression of the CD54 molecule.

The human IL-26 gene, IL26, maps to chromosome region 12q15 between two other important class-2 cytokine genes, IFNG (IFN-γ) and IL22 (IL-22) . Several reports have shown that the IL-26 gene is often co-expressed with IL-22 at high levels by Th17 cells.

However interleukin-26 is not going to do anthing to mice blood brain barrier as is the IL-26 gene is curiously absent in mice. But there is a IL-26 receptor and human IL-26 binds to it. It inhibits EAE

Does it pass the snack you in the eye test

Will it become a treatment….what do you think? It has to do better than natalizumab in terms of efficacy or side effect

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