Antigen-Presenting Cells in the Central Nervous System
The immune system employs a combination of innate and adaptive immune responses to detect and eliminate danger such as infiltrating pathogens or excessive tissue destruction. Antigen-presenting cells (APC), such as dendritic cells (DC) and Macrophages (MΦ), are crucial for initiating innate immune responses and processing of antigen to facilitate adaptive T cell-mediated immunity. DC and MΦ arise mostly from myeloid progenitors in that exit the bone marrow and populate the tissues where they finish their differentiation and, in some cases, still replicate. While both DC and MΦ function in antigen uptake, processing, and presentation, DC are the most efficient in priming naïve T cells and triggering antigen-specific effector T cells. APC are localized in all peripheral tissues and act as a first line of defense by sensing alterations in their microenvironment. In response to a pathogen or tissue injury, DC travel to the draining lymph node where they arrive with a mature phenotype characterized by, among others, the upregulation of costimulatory molecules, and the production of inflammatory cytokines. In the lymph nodes, DC are fully capable of presenting antigens to naïve T cells. Importantly, as they are delicate sensors of their microenvironment, APC also control immunological homeostasis in tissues, and can reduce excessive tissue destruction through an effective reduction of immune activation. APC are thus highly versatile innate immune cells, depending on the environmental signals, can either promote activation of inflammatory T cells or dampen immune responses, for example, via the induction of regulatory T cells. In this review, we focus on how APC in the central nervous system (CNS) exert this dual function of keeping both immunologic silence as well as activation with a specific focus on glycan-binding proteins.
KeywordsMultiple Sclerosis Dendritic Cell Experimental Autoimmune Encephalomyelitis Antigen Present Cell Cervical Lymph Node
Our work is financially supported by VENI NWO-ALW (grant 863.08.020) and VENI NWO-ZONMW ZonMw (grant 916.12.113), Dutch MS-Research Foundation (MS06–598 and MS05–560 567), and TIPharma TI-214.
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