「ミクログリアまつり」シンポジウム１ 国際神経化学会（ISN）／日本神経化学会（JSN）ジョイントシンポジウム
"Microglia Matsuri" Symposium 1, ISN-JSN Joint Symposium |
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| 2020/9/12 9:00～9:30 Zoom A
MM1-01
How gut bacteria modulate brain-resident immune cells
*Erny Daniel1
1. Institute of Neuropathology, University of Freiburg, Germany
*Daniel Erny1
1. Institute of Neuropathology, University of Freiburg, Germany
Among the myeloid cells in the central nervous system (CNS) microglia are the main representatives of the innate immune system. Recently, several endogenous and exogenous factors were identified that essentially shape the microglial phenotype during both steady-state and pathological conditions. On the one hand, microglia receive inputs from CNS-endogenous sources for example, via crosstalk with other glial cells and neurons but on the other hand microglia are also highly modulated by external signals. Among them, host microbiota constantly regulates microglial maturation and function via short-chain fatty acids.
| | 2020/9/12 9:30～10:00 Zoom A
MM1-02
T-cells modulate CSF1-microglia induced pain behavior in a sex specific manner
*Vainchtein Ilia D.1、Kuhn Julia A.2、Braz Joao2、Hamel Katherine2、Bernstein Mollie2、Ortiz-Carpena Jorge3、Molofsky Ari3、Molofsky Anna V.1、Basbaum Allan I.2
1. Department of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, USA.、2. Department of Anatomy, University of California, San Francisco, USA.、3. Department of Laboratory Medicine, University of California, San Francisco, USA.
*Ilia D. Vainchtein1, Julia A. Kuhn2, Joao Braz2, Katherine Hamel2, Mollie Bernstein2, Jorge Ortiz-Carpena3, Ari Molofsky3, Anna V. Molofsky1, Allan I. Basbaum2
1. Department of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, USA., 2. Department of Anatomy, University of California, San Francisco, USA., 3. Department of Laboratory Medicine, University of California, San Francisco, USA.
Peripheral nerve injury induces expression of colony-stimulating factor 1 (CSF1) in injured sensory neurons and mechanical hypersensitivity, a hallmark of neuropathic pain. We have found that intrathecal (i.t) injection of CSF1 is sufficient to induce mechanical hypersensitivity in male but not female mice. CSF1 is a myeloid growth factor whose primary target in the lumbar spinal cord are microglia. Previous studies have shown that microglia contribute to pain hypersensitivity. Interestingly, i.t. injection of CSF1 promotes not only proliferation, but also leads to microglia activation and loss of morphology complexity, most prominent in males. We transcriptionally profiled these spinal cord microglia and found that male but not female microglia have robust upregulation of immune activation genes involved in cytokine production, chemotaxis and cell adhesion and overall acquire a phenotype previously identified as ‘damage associated microglia'. In addition, male microglia downregulate many of their tissue supportive functions. To understand the source of these sex specific differences in microglia response, we examined the potential role of the adaptive immune system. We identified a robust expansion of lymphocyte populations in the spinal cord meninges in response to i.t. CSF1 injection. T-cell depletion was sufficient to produce CSF1 induced mechanical hypersensitivity in females. Ongoing work is identifying the role of specific T-cell subsets in CSF1 induced pain hypersensitivity. In conclusion, our data reveals that CSF1 activates microglia in a sex specific manner and that the adaptive immune system is involved in this process.
| | 2020/9/12 10:00～10:25 Zoom A
MM1-03
1細胞解析によって明らかになるマウスおよびヒトミクログリアの時空間的多様性
Single-cell analysis reveals spatial and temporal heterogeneity of microglia in human and mice
*増田 隆博1
1. 九州大学
*Takahiro Masuda1
1. Kyushu University
Microglia play essential roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system (CNS). These highly diverse and specialized functions in different situations may be achieved by subsets of microglia that already pre-exist in situ. However, until recently, little was known if there are subclasses of microglia spatially and temporally restricted in the CNS during development or disease, due to a lack of unbiased and high-throughput methods to assess microglia heterogeneity. The recent emergence of novel single-cell techniques, such as single-cell RNA sequencing, allows overcoming such limitations and revealing the surprising context-dependent heterogeneity of microglia in mice and human. Importantly, the appearance of context-dependent microglia states with their own specific transcriptional profiles has the potential to reveal new therapeutic targets. In this symposium, I will discuss the current knowledge about spatial, temporal and functional diversity of microglia during development, homeostasis and disease.
| | 2020/9/12 10:25～10:40 Zoom A
MM1-04
ミクログリア制御と脳機能
Strategies for disease control by microglial rebirth
*小泉 修一1
1. 山梨大学院医
*Schuichi Koizumi1
1. Dept Pharmacol, Interdisciplinary Grad Sch Med, Univ Yamanashi
When microglia sense changes in the brain environment, they significantly change their phenotype and play a major role in maintaining brain homeostasis and suppressing or exacerbating diseases. For example, microglia that detect a mild stroke acquire ischemic tolerance by sending the signals to astrocytes (from microglia to astrocytes), and although Alexander disease (AxD) is the primary astrocyte disease caused by mutations in GFAP, microglia that detect abnormalities in astrocytes transform into cytoprotective ones and suppress the deterioration of AxD (from astocytes to microglia). It has been reported that the CSF1R antagonist (ON) removes more than 95% of microglia from the brain and the CSF1R antagonist withdraws (OFF) cause repopulation of microglia. Number of repopulated microglia is almost same as that of control. However, microglial characteristic feature is changed by repopulation, and in AxD model mice, they become highly neuroprotective. These findings suggest that repopulation of microglia by CSF1R ON/OFF could be a new strategy for microglial control as well as that of brain diseases. In this symposium, we will discuss how microglia are altered by microglial ON/OFF and replacement, and how they affect various diseases.
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