Mohammad G. Mohammad, Vicky W. W. Tsai, Hui Li, Masoud Hassanpour, Prue Hart, Samuel N. Breit, Paul E. Sawchenko and David A. Brown
Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Sharjah, Sharjah, UAE
The ability of the central nervous system (CNS) to maintain immune privilege is well known, but poorly understood. However, it appears that in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), the cervical lymph nodes (CxLNs) may participate in this process. We therefore wished to establish whether there was immune cellular traffic from the CNS to the CxLNs, as well as its functional significance. Using IHC, dendritic cells (DCs) were more prominent throughout the rostral migratory stream (RMS), a pathway of neural stem cells. Further, DCs migrated from the RMS to the CxLNs, a process interrupted by Fingolimod treatment. This treatment led to the accumulation of DCs along the RMS and to severer actively induced EAE. The same treatment of 2D2 mice, a T-cell receptor transgenic mice, induced spontaneous with accumulation of antigen specific T-cells in the spinal cords of these EAE-resistant mice. In these mice, spinal cord T-cell infiltration was proportional to the ratio of anti-inflammatory T-regulatory cells (Tregs) to pro-inflammatory T-effector cells in their CxLNs. Investigating this phenomenon showed that RMS-Fingolimod treatment compromised CxLN Treg function. Using a delayed type hypersensitivity model, we demonstrate that the same treatment leads to fewer regulatory DCs in CxLNs. Combined; these data suggest that DCs migrate from the CNS to the CxLNs and regulate anti-CNS immunity representing a novel target for the treatment of CNS autoinflammatory disease.