Immune cell trafficking from the brain maintains CNS immune tolerance

Mohammad, Mohammad G., Tsai, Vicky W.W., Ruitenberg, Marc J., Hassanpour, Masoud, Li, Hui, Hart, Prue H., Breit, Samuel N., Sawchenko, Paul E. and Brown, David A. (2014) Immune cell trafficking from the brain maintains CNS immune tolerance. Journal of Clinical Investigation, 124 3: 1228-1241. doi:10.1172/JCI71544

Author Mohammad, Mohammad G.
Tsai, Vicky W.W.
Ruitenberg, Marc J.
Hassanpour, Masoud
Li, Hui
Hart, Prue H.
Breit, Samuel N.
Sawchenko, Paul E.
Brown, David A.
Title Immune cell trafficking from the brain maintains CNS immune tolerance
Journal name Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 2014-03-03
Year available 2014
Sub-type Article (original research)
DOI 10.1172/JCI71544
Open Access Status DOI
Volume 124
Issue 3
Start page 1228
End page 1241
Total pages 14
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Abstract In the CNS, no pathway dedicated to immune surveillance has been characterized for preventing the anti-CNS immune responses that develop in autoimmune neuroinflammatory disease. Here, we identified a pathway for immune cells to traffic from the brain that is associated with the rostral migratory stream (RMS), which is a forebrain source of newly generated neurons. Evaluation of fluorescently labeled leukocyte migration in mice revealed that DCs travel via the RMS from the CNS to the cervical LNs (CxLNs), where they present antigen to T cells. Pharmacologic interruption of immune cell traffic with the mononuclear cell-sequestering drug fmgolimod influenced anti-CNS T cell responses in the CxLNs and modulated experimental autoimmune encephalomyelitis (EAE) severity in a mouse model of multiple sclerosis (MS). Fingolimod treatment also induced EAE in a disease-resistant transgenic mouse strain by altering DC-mediated Treg functions in CxLNs and disrupting CNS immune tolerance. These data describe an immune cell pathway that originates in the CNS and is capable of dampening anti-CNS immune responses in the periphery. Furthermore, these data provide insight into how fmgolimod treatment might exacerbate CNS neuroinflarnmation in some cases and suggest that focal therapeutic interventions, outside the CNS have the potential to selectively modify anti-CNS immunity.
Keyword Immune tolerance
Neuroinflammatory disease
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID NS-21182
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Biomedical Sciences Publications
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