The crucial role of dendritic cells in rhinitis

KleinJan, Alex

doi:10.1097/aci.0b013e328342335f

Cited by 5 publications

(3 citation statements)

References 38 publications

(61 reference statements)

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“…Variants with cell-type-specific eQTL effects in the single-cell PBMC (scPBMC) data are enriched for disease-associated variants of nine immune-related traits (hF DR ≤ 5%). For example, variants with eQTL effects specific to conventional and plasmacytoid dendritic cells are enriched for allergic rhinitis-associated variants, consistent with the crucial role of dendritic cells in the development and maintenance of rhinitis [54]. In addition, variants with eQTL effects specific to B and CD4+…”

Section: Resultsmentioning

confidence: 61%

Fast and powerful statistical method for context-specific QTL mapping in multi-context genomic studies

Lü

Thompson

et al. 2021

Preprint

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Recent studies suggest that context-specific eQTLs underlie genetic risk factors for complex diseases. However, methods for identifying them are still nascent, limiting their comprehensive characterization and downstream interpretation of disease-associated variants. Here, we introduce FastGxC, a method to efficiently and powerfully map context-specific eQTLs by leveraging the correlation structure of multi-context studies. We first show via simulations that FastGxC is orders of magnitude more powerful and computationally efficient than previous approaches, making previously year-long computations possible in minutes. We next apply FastGxC to bulk multi-tissue and single-cell RNA-seq data sets to produce the most comprehensive tissue- and cell-type-specific eQTL maps to date. We then validate these maps by establishing that context-specific eQTLs are enriched in corresponding functional genomic annotations. Finally, we examine the relationship between context-specific eQTLs and human disease and show that FastGxC context-specific eQTLs provide a three-fold increase in precision to identify relevant tissues and cell types for GWAS variants than standard eQTLs. In summary, FastGxC enables the construction of context-specific eQTL maps that can be used to understand the context-specific gene regulatory mechanisms underlying complex human diseases.

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Section: Resultsmentioning

confidence: 61%

Fast and powerful statistical method for context-specific QTL mapping in multi-context genomic studies

Lü

Thompson

et al. 2021

Preprint

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“…However, we cannot eliminate paracellular or cell autonomous movement of prions, as has previously been shown [26], [59]. Inhalation of dust and other particles has been shown to cause rhinitis that enhances cytokines and increases the number of DCs in the nasal mucosa [55], [60]–[62].…”

Section: Discussionmentioning

confidence: 91%

Intranasal Inoculation of White-Tailed Deer (Odocoileus virginianus) with Lyophilized Chronic Wasting Disease Prion Particulate Complexed to Montmorillonite Clay

et al. 2013

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Chronic wasting disease (CWD), the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte), lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

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“…Introduction of carboxyfluorescein succinimidyl ester (CFSE)-labeled DCs or DiY Dye in the nasal mucosa in droplet form resulted in detectable CFSE-labeled DCs and DiY in the nasal mucosa in the nasal-associated lymphoid tissue (NALT) and in the cervical LN, which drains the nose. No CFSE-labeled cells could be detected in either the mediastinal LN or the lung (35). In a human migration study of the respiratory tract, it is indicated that antigen pulsed DCs that are introduced by injection in the nasal inferior turbinates can be traced back to the regional LNs (36).…”

Section: Migration From Peripheral Tissue To the Draining Lnmentioning

confidence: 99%