scRNAseq data for Filaggrin deficiency in mice alters the early life CD4+ T cell response to skin commensal bacteria Gonzalez et al

Published: 14 November 2022| Version 1 | DOI: 10.17632/64shh39z76.1
Contributors:
Jeanmarie Gonzalez,
Tiffany Scharschmidt

Description

Filaggrin deficiency in mice alters the early life CD4+ T cell response to skin commensal bacteria Filaggrin mutations underlie ichthyosis vulgaris and increased risk of atopic dermatitis, conditions typified by disruption of the skin microbiome and cutaneous immune response. Yet, it remains unclear if neonatal skin barrier compromise due to filaggrin deficiency alters the quality of commensal-specific T cells and the functional impact of such responses. To address these questions, we profiled changes in the skin barrier and early cutaneous immune response of neonatal C57BL/6 Flg-/- and WT mice using scRNAseq, flow cytometry and other modalities. Flg-/- neonates showed little alteration in transepidermal water loss or lipid or corneocyte related gene expression. However, they demonstrated increases in barrier disruption genes, epidermal dye penetration and numbers of skin CD4+ T cells. Using an engineered strain of Staphylococcus epidermidis (S. epi-2W) to study the response to neonatal skin colonization, we found that commensal-specific CD4+ T cells were skewed in Flg-/- pups towards effector rather than regulatory T cells. This altered response persisted into adulthood, where it was typified by Th17 cells and associated with increased susceptibility to imiquimod-induced skin inflammation. Thus, subtle but impactful differences in neonatal barrier function in Flg-/- mice are accompanied by a skewed commensal-specific CD4+ response, with enduring consequences for skin immune homeostasis. Our goal was to analyze epidermal subsets in the skin of neonatal wildtype and filaggrin deficient mice colonized with Staphylococcus epidermidis Mice were colonized with Staphylococcus epidermidis D7/10 of life, harvested D12. Skin was harvested and digested with trypsin to enrich for epidermal cells before single cell RNAseq was performed. JRG01 is cells from WT mice and JRG02 is cells from Flg-/- (filaggrin KO) mice . Specs: mRNA, paired-end, NovaSeq 6000, Paired end (28,8,0,91) cycling condition, S2 flowcell Novaseq 6000 version1.5 kit, Chromium Single Cell 3' Reagent Kits V3, Cell Ranger v 3.0.2, mm10 10x Genomics output files: barcodes.tsv.gz, features.tsv.gz, matrix.mtx.gz

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Institutions

University of California San Francisco

Categories

Immunology, Microbiology, Dermatology

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