IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis

• Published in: Journal of neuroimmunology Vol. 332; pp. 147 - 154
• Main Authors: Setiadi, A. Francesca, Abbas, Alexander R., Jeet, Surinder, Wong, Kit, Bischof, Antje, Peng, Ivan, Lee, James, Bremer, Meire, Eggers, Erica L., DeVoss, Jason, Staton, Tracy, Herman, Ann, von Büdingen, H. -Christian, Townsend, Michael J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.07.2019
• Subjects: Adult; Aged; Animals; Blood-Brain Barrier; Cells, Cultured; Encephalomyelitis, Autoimmune, Experimental - physiopathology; Encephalomyelitis, Autoimmune, Experimental - therapy; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Female; Humans; Immunization, Passive; Interleukin-17 - antagonists & inhibitors; Interleukin-17 - cerebrospinal fluid; Interleukin-17 - physiology; Interleukin-6 - pharmacology; Mice; Mice, Inbred C57BL; Middle Aged; Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid; Multiple Sclerosis, Relapsing-Remitting - physiopathology; Receptors, Interleukin-6 - physiology; Recombinant Proteins - pharmacology; Young Adult; Qalb; RRMS; LLOQ; BBB; MRI; CNS; LY; NFL; CSF; qPCR; dpi; Th17; EDSS; PBS; MEFs; MOG; Rw; MS; EAE; i.p; BCP; GFAP; Mab; OCB; TNF-α; rh; TJ; IL-17; TEER; rm; HD; Gd; CFA
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2019.04.011

IL-17 has been implicated in the pathogenesis of multiple sclerosis (MS). Here, we show that blockade of IL-17A, but not IL-17F, attenuated experimental autoimmune encephalomyelitis (EAE). We further show that IL-17A levels were elevated in the CSF of relapsing-remitting MS (RRMS) patients and that they correlated with the CSF/serum albumin quotient (Qalb), a measure of blood-brain barrier (BBB) dysfunction. We then demonstrated that the combination of IL-17A and IL-6 reduced the expression of tight junction (TJ)-associated genes and disrupted monolayer integrity in the BBB cell line hCMEC/D3. However, unlike IL-17A, IL-6 in the CSF from RRMS patients did not correlate with Qalb. These data highlight the potential importance of targeting IL-17A in preserving BBB integrity in RRMS. [Display omitted] •IL-17A, but not IL-17F, contributes to EAE pathogenesis.•IL-17A, but not IL-17F, is elevated in RRMS CSF.•CSF IL-17A levels correlate with blood-brain barrier damage in RRMS.•A combination of IL-17A and IL6 impairs endothelium tight junction gene expression and monolayer integrity.