Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases

The central nervous system (CNS) is now known to actively communicate with the immune system to control immune responses both centrally and peripherally. Within the CNS, while studies on glial cells, especially microglia, have highlighted the importance of this cell type in innate immune responses of the CNS, the immune regulatory functions of other cell types, especially neurons, are largely unknown. How neuroimmune cross-talk is homeostatically maintained in neurodevelopment and adult plasticity is even more elusive. Inspiringly, accumulating evidence suggests that neurons may also actively participate in immune responses by controlling glial cells and infiltrated T cells. The potential clinical application of this knowledge warrants a deeper understanding of the mutual interactions between neurons and other types of cells during neurological and immunological processes within the CNS, which will help advance diagnosis, prevention, and intervention of various neurological diseases. The aim of this review is to address the immune function of both glial cells and neurons, and the roles they play in regulating inflammatory processes and maintaining homeostasis of the CNS.Peer reviewe

Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

Background: In a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-?-his-dipeptidase as candidate biomarkers associated with the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Here, we aimed to validate these results in individual CSF samples using alternative techniques. Methods: In a first replication study, levels of apolipoproteins AI and AIV, vitronectin, and plasminogen were measured by ELISA in CSF and serum of 56 CIS patients (29 patients who converted to CDMS (MS converters) and 27 patients who remained with CIS during follow-up (MS non-converters)) and 26 controls with other neurological disorders. Semaphorin 7A and ala-?-his-dipeptidase levels were determined by selected reaction monitoring (SRM) in CSF of 36 patients (18 MS converters, 18 non-converters) and 20 controls. In a second replication study, apolipoprotein AI levels were measured by ELISA in CSF of 74 CIS patients (47 MS converters, 27 non-converters) and 50 individual controls, and levels of semaphorin 7A and ala-beta-his-dipeptidase were determined by SRM in 49 patients (24 MS converters, 25 non-converters) and 22 controls. Results: CSF levels of apolipoprotein AI were increased (P = 0.043) and levels of semaphorin 7A and ala-?-his-dipeptidase decreased (P = 4.4?×?10?10 and P = 0.033 respectively) in MS converters compared to non-converters. No significant differences were found in serum levels for apolipoproteins AI and AIV, vitronectin, and plasminogen. Findings with semaphorin 7A and ala-?-his-dipeptidase were also validated in the second replication study, and CSF levels for these two proteins were again decreased in MS converters versus non-converters (P = 1.2?×?10?4 for semaphorin 7A; P = 3.7?×?10?8 for ala-?-his-dipeptidase). Conversely, apolipoprotein AI findings were not replicated and CSF levels for this protein did not significantly differ between groups. Furthermore, CSF semaphorin 7A levels were negatively associated with the number of T2 lesions at baseline and one-year follow-up. Conclusions: These results validate previous findings for semaphorin 7A and ala-?-his-dipeptidase, and suggest that these proteins play a role as CSF biomarkers associated with the conversion to CDMS in CIS patients.This work was supported by a grant from the 'Fondo de Investigación Sanitaria' (FIS) (grant number PI09/00788), Ministry of Science and Innovation, Spain. EC is supported by a contract from the FIS (contract number FI 09/00705), Ministry of Science and Innovation, Spai