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RNA-seq analysis comparing primary NKTL sample over tonsil control

ABSTRACT: RNA-seq analysis comparing primary NKTL sample over tonsil control

PROVIDER: PRJNA788941 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17260121_1.fastq.gz	Fastqsanger.gz
	SRR17260121_2.fastq.gz	Fastqsanger.gz
	SRR17260122_1.fastq.gz	Fastqsanger.gz
	SRR17260122_2.fastq.gz	Fastqsanger.gz
	SRR17260123_1.fastq.gz	Fastqsanger.gz

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RNA-seq analysis comparing primary NKTL sample over tonsil control

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Project description:CD4+ regulatory T cells (Tregs) are key orchestrators of the immune system, fostering the establishment of protective immunity while preventing deleterious responses. Infancy and childhood are crucial periods of rapid immunologic development but how Tregs mediate immune responses at these earliest timepoints of human life is poorly understood. Here we compare blood and tissue (tonsil) Tregs across pediatric and adult subjects to investigate age related differences in Treg biology. We observed increased FoxP3 expression and proportions of Tregs in tonsil compared to paired blood samples in children. Within tonsil, early life Tregs accumulated in extrafollicular regions with cellular interactions biased towards CD8+ T cells. Tonsil Tregs in both children and adults expressed transcriptional profiles enriched for lineage defining signatures and canonical functionality compared to blood, suggesting tissue as the primary site of Treg activity. Early life tonsil Tregs transcriptional profiles were further defined by pathways associated with activation, proliferation, and polyfunctionality. Observed differences in pediatric tonsil Treg transcriptional signatures were associated with phenotypic differences, high proliferative capacity and robust production of IL-10 compared to adult Tregs. These results identify tissue as a major driver of Treg identity, provide new insights into developmental differences in Treg biology across the human lifespan and demonstrate unique functional properties of early life Tregs.

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Project description:To study characteristics of the orapharyngeal epithelia which may influence susceptibility or resistance to HIV, we performed microarray analysis of the tonsil and gingival epithelium.Tonsil epithelium has been implicated in HIV pathogenesis, but its role in oral transmission remains controversial. We performed microarray analysis of Laser Capture Microdissected tonsil and gingival epithelium. Our data revealed that genes related to immune functions such as antibody production and antigen processing were increasingly expressed in tonsil compared to the epithelium of another oro-pharyngeal site, gingival epithelium. Importantly, tonsil epithelium highly expressed genes associated with HIV entrapment and/or transmission, including the HIV co-receptor CXCR4 and the potential HIV binding molecules, FcRγIII, complement receptor 2, and various complement components. This increased expression of molecules involved in viral recognition, binding and entry may favor virus-epithelium interaction in an environment with reduced innate anti-viral mechanisms. Specifically, secretory leukocyte protease inhibitor, an innate molecule with anti-HIV activity, was minimal in the tonsil epithelium, in contrast to oral mucosa. Collectively, our data suggest that increased expression of molecules associated with HIV binding and entry coupled with decreased innate anti-viral factors may render the tonsil a potential site for oral transmission. Keywords: Cross sectional

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