In many forms of retinal degenerative diseases in human, microglia relocate to and accumulate in the subretinal space. However, the roles of microglia in retinal degeneration are poorly understood. By leveraging single cell RNA-seq, we identified a distinct microglia subtype in the subretinal space. These microglia underwent transcriptional reprogramming characterized by reduced expression of homeostatic checkpoint genes and upregulation of injury-responsive genes. Importantly, this transition is associated with protection of the retinal pigment epithelium from damage caused by disease. Therefore, our data demonstrated microglial heterogeneity in retinal degeneration and may provide important implications for developing new strategies to prevent loss of vision. Overall design: Transcriptional profiling of Cx3cr1+ single cells from the mouse model of light-induced retinal degeneration with matched control, generated from single cell RNA-sequencing of over 10,000 cells.
Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.
Specimen part, Cell line, Subject
View SamplesSkin conventional dendritic cells (cDC) exist as two distinct subsets, cDC1 and cDC2, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here we examined the roles of dermal cDC1 and cDC2 during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1, but not cDC2, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine VEGFa by a minor subset of activated EpCAM+CD59+Ly6D+ cDC1. Neutrophil recruitment by dermal cDC1 was also observed during S. aureus, BCG or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1 are essential regulators of the innate response in cutaneous immunity, with roles beyond classical antigen presentation. Overall design: Examined the effect of cDC1 (CD103+DC) depletion on neutrophils infiltrating the skin during P. acnes infection.
A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.
Specimen part, Treatment, Subject
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