It seems conceivable that microglia play a key role in CNS disorders, in accordance with their capacity to rapidly detect CNS disturbance and their contribution to innate and adaptive immune responses through a.o. phagocytosis and antigen presentation. Although it is tempting to speculate that microglia principally protect the CNS, studies on CNS disorders imply that microglia activity can be both beneficial and detrimental. Currently, the main challenge appears to be linkage of microglia phenotype and function, as indicators of microglia activity, to initiation, course and outcome of CNS disorders. Our finding that microglia express CCR7 after antigen uptake indicates that they may be able to migrate towards sources of CCL19 and CCL21 within the CNS or towards lymph nodes outside the CNS before presenting antigen. This migration may be an important link to the adaptive immune response and, therefor, be a target for intervention. In addition, migration outside the CNS may render the adaptive immune response more accessible for therapeutic intervention. Our newly developed microglia isolation protocol may be a valuable tool for determination of microglia phenotype and function in both the healthy CNS and in CNS disorders since it yields microglia in high number and purity for accurate and convenient ex vivo analysis. The protocol allowed us to show immunological diversity among microglia from various regions of the healthy, adult mouse CNS. This microglia diversity may play a role in region-specific CNS disorders by influencing the way mircroglia respond to damage. Our findings can form an incentive for future studies concerning diversity in microglia phenotype and function. Microglia diversity may probably depend on interaction with surrounding cells and other environmental signals. We reviewed chemokines expressed and secreted by neurons and discussed their role in neuoprotective and detrimental activity of microglia in CNS disorders, which warrants further exploration of the role of these neuronal chemokines in CNS cell interaction and in particular their effect on microglia activity. Increasing insight into microglia phenotype and function diversity is likely to offer a lead for the development of therapeutic strategies that selectively promote neuroprotective microglia activity and suppress detrimental microglia activity in CNS disorders.
|Kwalificatie||Doctor of Philosophy|
|Status||Published - 2007|