シンポジウム
41 脳内免疫の新時代：多様な免疫細胞が作り上げる脳内環境と疾患治療標的としての可能性
41 A new era in CNS immunity: a wide variety of immune cells governs brain environment. A potential target for therapeutics
座長：増田 隆博（九州大学大学院薬学研究院薬理学分野）・伊藤 美菜子（九州大学生体防御医学研究所アレルギー制御学分野） |
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| 2022年6月30日 14:00～14:30 沖縄コンベンションセンター 会議場B1 第3会場
1S03a-01
Phenotype and origin of meningeal B cells
*Simone Brioschi(1)
1. Washington University in St. Louis
Keyword: Meningeal immunity, B cells, Aging
The central nervous system (CNS) is enveloped by the meninges, which harbor different immune cell types that provide constant surveillance at the CNS border. Recent studies have described the origin and diversity of the myeloid cell landscape at the CNS interfaces. B cells represent a major immune cell type in mouse meninges; however, their origin and phenotype have been poorly investigated. Through single cell analyses, confocal imaging, bone marrow chimeras and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, the bone marrow niche within the flat bones of the skull. Calvaria-derived B cells encompass multiple stages of B cell development and reach the meninges through specialized vascular connections. Early B cells may complete their maturation within the meningeal compartment, wherein dura fibroblasts can provide critical molecules for B cell development, such as CXCL12. In aged mice, however, a population of age-associated B cells (ABCs) infiltrates the mouse meninges from the circulation. Based on BCR repertoire analysis, blood-borne ABCs locally undergo terminal differentiation into Ig-secreting plasma cells, which accumulate in the aged meninges. We suggested that the calvaria may provide the meningeal compartment with a constant supply of B cells educated by CNS-derived antigens, thus preventing the generation of immunoglobulins with high affinity for CNS epitopes. This study provides new insights on the origin and features of meningeal B cells in homeostasis and aging. | | 2022年6月30日 14:30～15:00 沖縄コンベンションセンター 会議場B1 第3会場
1S03a-02
多様なマクロファージが作り出す脳内環境
Diverse macrophages govern brain environment
*増田 隆博(1)
1. 九州大学大学院薬学研究院
*Takahiro Masuda(1)
1. Grad Sch Pharm, Kyushu University, Fukuoka, Japan
Keyword: microglia, macrophage, heterogeneity, CNS
The central nervous system (CNS) host a variety of immune cells, which carry out various functions during not only neural development and homeostasis, but in disease conditions. Macrophages in the CNS comprise two anatomically distinct populations: microglia are located in the parenchyma, and CNS border-associated macrophages (CAMs) are found in CNS interfaces including the meninges, perivascular space, and choroid plexus. Both of them contribute to a specialized and tightly regulated resident immune system in the CNS. Accumulating evidence has shown that microglia play a variety of biologically important roles—such as supporting neurogenesis, synaptic pruning, scavenging for dying cells in the CNS, whereas less is known so far about the function of CAMs during homeostasis and diseases. In contrast, the recent emergence of novel technologies, such as single-cell RNA sequencing and fate mapping, has enabled the profiling of microglia and CAMs, and revealing previously-unknown spatio-temporal diversity. In this symposium, I will discuss our current knowledge of the origins, kinetics, functions, transcriptomic profiles, heterogeneity of microglia and CAMs, with a main focus on recent findings, and how those macrophages regulate the CNS environment. | | 2022年6月30日 15:00～15:30 沖縄コンベンションセンター 会議場B1 第3会場
1S03a-03
Brain borders at the central stage of neuroimmunology
*Justin Rustenhoven(1,2)
1. Washington University in St Louis, MO, USA, 2. The University of Auckland, New Zealand
Keyword: Skull bone marrow, Meninges, Neuroinflammation, Brain
Our immune system and central nervous system (CNS) continuously surveil the environment and make on-demand adjustments to maintain homeostasis. Yet despite their commonalities, these systems were originally believed to be entirely separate from one another—leading to a long-held dogma of CNS immune privilege. Our research has recently uncovered numerous unique anatomical features of the brain borders that permit functional immunological interactions between these two systems. We demonstrate that the brain borders contain a vascular stromal niche highly permissive for immune trafficking, facilitating an immunological hub that continuously surveys CNS antigens present in the cerebrospinal fluid. Further, we demonstrate how this recognition of CNS matter at the brain borders can mobilize cells from the overlying skull bone marrow—an active hematopoietic site that directly supplies myeloid and lymphoid populations to the brain borders and brain itself during various pathologies via direct bone marrow-to-meningeal channels. Finally, we demonstrate how the skull bone marrow itself can continuously detect for CNS pathology via direct connection with the cerebrospinal fluid which shapes hematopoiesis during immune responses. Collectively, these data uncover novel immunological roles for the CNS borders during homeostasis and disease, in order to detect brain dysfunction and mount a tailored and targeted response. | | 2022年6月30日 15:30～16:00 沖縄コンベンションセンター 会議場B1 第3会場
1S03a-04
Elucidation of immune cell dynamics after ischemic stroke
*Minako Ito(1)
1. MIB, Kyushu Univ, Fukuoka, Japan
Keyword: Ischemic stroke, Immune cells
Acute and chronic inflammation are complicatedly involved in various central nervous system diseases. It has been reported that not only multiple sclerosis and anti-NMDA receptor antibody encephalitis but also neurological diseases such as Parkinson's disease and Alzheimer are associated with inflammation. It has also been strongly suggested that autism and schizophrenia are associated with the immune system. The elucidation of the interaction between immune cells and glial cells and nerve cells in the central nervous system is also important problems in the development of therapeutic / preventive methods for various central nervous system diseases. In the acute and subacute phases of ischemic stroke, innate immune cells including macrophages infiltrate into the brain and cause prolonged inflammation and worsening of neurological symptoms. Moreover, it has been clarified that much more T cells infiltrate into the brain during the chronic phase after stroke than in the acute phase. Mice with a cerebral infarction are resistant to recurrence of cerebral infarction, which is “ischemic tolerance”. In order to elucidate the mechanism of the resistance, we performed bulk-RNA sequencing and single cell RNA sequencing of brain cells in the acute phase, chronic phase, and contralateral side of infarct region. The population of immune cells and brain-resident cells in the brain changed dramatically after stroke. Interestingly, changes in cell population and gene expression were observed not only on the infarct side but also on the opposite side. Furthermore, it was suggested that the serum in acute phase, and the serum and blood cells in the chronic phase are important to acquire tolerance. These data suggest that damage tolerance to recurrence of ischemic stroke may affect not only the infarct region but also the contralateral side via serum and immune cells after brain injury. In addition, we clarified the significance of immune cells in the chronic phase of cerebral infarction from both brain and dura. | |
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