IL-17A Facilitates Entry of Autoreactive T-Cells and Granulocytes into the CNS During EAE
-
Published:2023-03-01
Issue:3
Volume:25
Page:350-359
-
ISSN:1535-1084
-
Container-title:NeuroMolecular Medicine
-
language:en
-
Short-container-title:Neuromol Med
Author:
Zimmermann JulianORCID, Nitsch LouisaORCID, Krauthausen Marius, Müller Marcus
Abstract
AbstractInterleukin-17A plays a crucial role in multiple sclerosis and other autoimmune diseases. Although the link between IL-17 and disease activity has been clearly demonstrated, the precise function of this cytokine remains elusive. Here, we investigated the function of astrocyte-targeted IL-17A production in GF/IL-17 transgenic mice during EAE. In particular, IL-17A is important during disease induction. In mice with transgenic IL-17A production, disease occurs earlier and peak disease is more severe, whereas remission is unimpaired. IL-17A synthesis is associated with increased infiltration of granulocytes into the CNS and microglial activation. Moreover, IL-17A synthesis allows induction of MOG-EAE without the additional administration of the co-adjuvant pertussis toxin. Examination of double transgenic GF/IL-17 2D2 mice revealed that, in addition, local IL-17A production facilitates spontaneous infiltration of immune cells into the CNS in mice expressing a MOG-specific T-cell receptor. Overall, we provide evidence for a crucial effect of IL-17A in the induction phase of EAE, facilitating the infiltration of granulocytes and autoreactive T-cells into the CNS.
Funder
Rheinische Friedrich-Wilhelms-Universität Bonn Universitätsklinikum Bonn
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Molecular Medicine
Reference47 articles.
1. Bedarf, J. R., Beraza, N., Khazneh, H., Özkurt, E., Baker, D., Borger, V., Wüllner, U., & Hildebrand, F. (2021). Much ado about nothing? Off-target amplification can lead to false-positive bacterial brain microbiome detection in healthy and Parkinson’s disease individuals. Microbiome, 9(1), 75. https://doi.org/10.1186/s40168-021-01012-1 2. Bettelli, E., Pagany, M., Weiner, H. L., Linington, C., Sobel, R. A., & Kuchroo, V. K. (2003). Myelin oligodendrocyte glycoprotein–specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis. Journal of Experimental Medicine, 197(9), 1073–1081. https://doi.org/10.1084/jem.20021603 3. Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., Zurawski, S., Wiekowski, M., Lira, S. A., Gorman, D., Kastelein, R. A., & Sedgwick, J. D. (2003). Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature, 421(6924), 744–748. https://doi.org/10.1038/nature01355 4. Cua, D. J., & Tato, C. M. (2010). Innate IL-17-producing cells: The sentinels of the immune system. Nature Reviews Immunology, 10(7), 479–489. https://doi.org/10.1038/nri2800 5. Dumas, A., Amiable, N., de RiveroVaccari, J. P., Chae, J. J., Keane, R. W., Lacroix, S., & Vallières, L. (2014). The inflammasome pyrin contributes to pertussis toxin-induced IL-1β synthesis, neutrophil intravascular crawling and autoimmune encephalomyelitis. PLoS Pathogens, 10(5), 1004150. https://doi.org/10.1371/journal.ppat.1004150
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|