Humoral immunity at the brain borders in homeostasis

Posner, David A; Lee, Colin Y C; Portet, Anaïs; Clatworthy, Menna R.

doi:10.1016/j.coi.2022.102188

Cited by 8 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are only at the beginning of understanding the role of the relatively newly described B cell niches in the meninges and the skull bone marrow [ 13 ]. Most of the work to date in this area has been carried out using mouse models.…”

Section: Future Perspectivesmentioning

confidence: 99%

B Lymphocytes in Parkinson’s Disease

Scott

2022

JPD

View full text Add to dashboard Cite

It is well known that B lymphocytes differentiate into plasma cells that produce antibodies. B cells also perform a number of less well-known roles including antigen presentation, regulation of T cells and innate immune cells, cytokine production, and maintenance of subcapsular sinus macrophages. Given that there is clear evidence of inflammation in Parkinson’s disease (PD) both in the central nervous system and in the periphery, it is almost certain that B lymphocytes are involved. This involvement is likely to be complicated given the variety of roles B cells play via a number of distinct subsets. They have received less attention to date than their counterparts, T cells, and monocytes. B lymphocytes are decreased in PD overall with some limited evidence that this may be driven by a decrease in regulatory subsets. There is also evidence that regulatory B cells are protective in PD. There is evidence for a role played by antibodies to alpha-synuclein in PD with a possible increase in early disease. There are many exciting potential future avenues for further exploration of the role of B lymphocytes including improving our understanding of the role of meningeal and calvarial (skull bone marrow) based B cells in health and disease, the use of larger, well phenotyped clinical cohorts to understand changes in peripheral and cerebrospinal fluid B cells over time and the potential application of B cell targeted therapies in PD.

show abstract

Section: Future Perspectivesmentioning

confidence: 99%

B Lymphocytes in Parkinson’s Disease

Scott

2022

JPD

View full text Add to dashboard Cite

show abstract

“…The maximal human Bottom 200 (158/200) belonged to the repressive nuclear receptor NCOR1 in a comparison between profiles generated from tissue atlas resources (Uhlén et al, 2015; The Tabula Sapiens Consortium et al, 2022). The highest Mouse Top 200 (150/200) was associated with E2f8 , derived from two studies of the blood-brain barrier; one of these datasets, in combination with a study on the aging brain, also contributed to Elk3 having the highest Bottom 200 score of 149/200 (Kaya et al, 2022; Posner et al, 2022; van Lengerich et al,. 2023).…”

Section: Resultsmentioning

confidence: 99%

Identifying Reproducible Transcription Regulator Coexpression Patterns with Single Cell Transcriptomics

Morin,

Chu,

Pavlidis

2024

Preprint

View full text Add to dashboard Cite

The proliferation of single cell transcriptomics has potentiated our ability to unveil patterns that reflect dynamic cellular processes, rather than cell type compositional effects that emerge from bulk tissue samples. In this study, we leverage a broad collection of single cell RNA-seq data to identify the gene partners whose expression is most coordinated with each human and mouse transcription regulator (TR). We assembled 120 human and 103 mouse scRNA-seq datasets from the literature, constructing a single cell coexpression network for each. We aimed to understand the consistency of TR coexpression profiles across a broad sampling of biological contexts, rather than examine the preservation of context-specific networks. Our workflow therefore explicitly prioritizes the patterns that are most reproducible across cell types, helping to characterize each TR's coexpression patterns. Towards this goal, we quantify the similarity of TR coexpression profiles within and across species, characterizing the consistency of each TR's coexpression across datasets. We create single cell coexpression rankings for each TR, demonstrating that this aggregated information recovers literature curated targets on par with ChIP-seq data. We then combine the coexpression and ChIP-seq information to identify candidate regulatory interactions supported across methods and species. Finally, we highlight interactions for the important neural TR ASCL1 to demonstrate how our compiled information can be adopted for community use.

show abstract

“…Therefore, the cell type deconvolution tool spSeudoMap was used to compensate for this discrepancy [ 50 ]. For lymphoid and myeloid brain cell types, scRNAseq samples from CNS border immune cells were used [ 119 ], and for microglia, scRNAseq samples from brain immune cells were used [ 89 ]. The distribution of representative cell types that showed significant differences between wild-type and 5xFAD mice was evaluated: homeostatic microglia, reactive microglia, macrophages, monocytes, dendritic cells, innate lymphoid cells, natural killer cells, and T cells.…”

Section: Methodsmentioning

confidence: 99%

Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model

Lee,

Suh,

Choi

et al. 2024

BMC Genomics

View full text Add to dashboard Cite

Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer’s disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics.

show abstract

Humoral immunity at the brain borders in homeostasis

Cited by 8 publications

References 45 publications

B Lymphocytes in Parkinson’s Disease

B Lymphocytes in Parkinson’s Disease

Identifying Reproducible Transcription Regulator Coexpression Patterns with Single Cell Transcriptomics

Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model

Contact Info

Product

Resources

About