scholarly journals High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease

Immunity ◽  
2018 ◽  
Vol 48 (3) ◽  
pp. 599 ◽  
Author(s):  
Dunja Mrdjen ◽  
Anto Pavlovic ◽  
Felix J. Hartmann ◽  
Bettina Schreiner ◽  
Sebastian G. Utz ◽  
...  
Immunity ◽  
2018 ◽  
Vol 48 (2) ◽  
pp. 380-395.e6 ◽  
Author(s):  
Dunja Mrdjen ◽  
Anto Pavlovic ◽  
Felix J. Hartmann ◽  
Bettina Schreiner ◽  
Sebastian G. Utz ◽  
...  

2021 ◽  
pp. 107385842199226
Author(s):  
Stellina Y. H. Lee ◽  
Nathanael J. Yates ◽  
Susannah J. Tye

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson’s disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.


2020 ◽  
Author(s):  
Haoyu Ruan ◽  
Zhe Wang ◽  
Yue Zhai ◽  
Ying Xu ◽  
Linyu Pi ◽  
...  

AbstractDiffuse large B-cell lymphoma (DLBCL) is the predominant type of central nervous system lymphoma (CNSL) including primary CNSL and secondary CNSL. Diffuse large B cells in cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of CNSL leptomeningeal involvement. To explore the distinct phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of 902 CSF-DLBCs from six CNSL-DLBCL patients using single-cell RNA sequencing technology. We defined CSF-DLBCs based on abundant expression of B-cell markers, as well as the enrichment of cell proliferation and energy metabolism pathways. CSF-DLBCs within individual patients exhibited monoclonality with similar variable region of light chains (VL) expression. It is noteworthy that we observed some CSF-DLBCs have double classes of VL (lambda and kappa) transcripts. We identified substantial heterogeneity in CSF-DLBCs, and found significantly greater among-patient heterogeneity compared to among-cell heterogeneity within a given patient. The transcriptional heterogeneity across CSF-DLBCs is manifested in cell cycle state and cancer-testis antigens expression. Our results will provide insight into the mechanism research and new diagnostic direction of CNSL-DLBCL leptomeningeal involvement.


2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.


2020 ◽  
Vol 6 (3) ◽  
pp. eaay6324 ◽  
Author(s):  
Jason R. Plemel ◽  
Jo Anne Stratton ◽  
Nathan J. Michaels ◽  
Khalil S. Rawji ◽  
Eric Zhang ◽  
...  

Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its “immune privileged” status.


2018 ◽  
Vol 25 (3) ◽  
pp. 227-240 ◽  
Author(s):  
Mithilesh Kumar Jha ◽  
Myungjin Jo ◽  
Jae-Hong Kim ◽  
Kyoungho Suk

Microglia-astrocyte crosstalk has recently been at the forefront of glial research. Emerging evidence illustrates that microglia- and astrocyte-derived signals are the functional determinants for the fates of astrocytes and microglia, respectively. By releasing diverse signaling molecules, both microglia and astrocytes establish autocrine feedback and their bidirectional conversation for a tight reciprocal modulation during central nervous system (CNS) insult or injury. Microglia, the constant sensors of changes in the CNS microenvironment and restorers of tissue homeostasis, not only serve as the primary immune cells of the CNS but also regulate the innate immune functions of astrocytes. Similarly, microglia determine the functions of reactive astrocytes, ranging from neuroprotective to neurotoxic. Conversely, astrocytes through their secreted molecules regulate microglial phenotypes and functions ranging from motility to phagocytosis. Altogether, the microglia-astrocyte crosstalk is fundamental to neuronal functions and dysfunctions. This review discusses the current understanding of the intimate molecular conversation between microglia and astrocytes and outlines its potential implications in CNS health and disease.


2018 ◽  
Vol 196 ◽  
pp. 158-164 ◽  
Author(s):  
S.K. Totsch ◽  
R.Y. Meir ◽  
R.M. Orlandella ◽  
L.A. Norian ◽  
R.E. Sorge

2020 ◽  
Author(s):  
Dunja D. Bijelić ◽  
Katarina D. Milićević ◽  
Milica N. Lazarević ◽  
Djordje M. Miljković ◽  
Jelena J. Bogdanović Pristov ◽  
...  

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