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Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney
Garrett S. Dunlap, … , J. Michelle Kahlenberg, Deepak A. Rao
Garrett S. Dunlap, … , J. Michelle Kahlenberg, Deepak A. Rao
Published March 15, 2022
Citation Information: JCI Insight. 2022;7(8):e156341. https://doi.org/10.1172/jci.insight.156341.
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Resource and Technical Advance

Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney

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Abstract

Cutaneous lupus is commonly present in patients with systemic lupus erythematosus (SLE). T cells have been strongly suspected to contribute to the pathology of cutaneous lupus; however, our understanding of the relevant T cell phenotypes and functions remains incomplete. Here, we present a detailed single-cell RNA-Seq profile of T and NK cell populations present within lesional and nonlesional skin biopsies of patients with cutaneous lupus. T cells across clusters from lesional and nonlesional skin biopsies expressed elevated levels of IFN-simulated genes (ISGs). Compared with T cells from control skin, however, T cells from cutaneous lupus lesions did not show elevated expression profiles of activation, cytotoxicity, or exhaustion. Integrated analyses indicated that skin lymphocytes appeared less activated and lacked the expanded cytotoxic populations prominent in lupus nephritis kidney T/NK cells. Comparison of skin T cells from lupus and systemic sclerosis skin biopsies further revealed an elevated ISG signature specific to cells from lupus biopsies. Overall, these data represent the first detailed transcriptomic analysis to our knowledge of the T and NK cells in cutaneous lupus at the single-cell level and have enabled a cross-tissue comparison that highlights stark differences in composition and activation of T/NK cells in distinct tissues in lupus.

Authors

Garrett S. Dunlap, Allison C. Billi, Xianying Xing, Feiyang Ma, Mitra P. Maz, Lam C. Tsoi, Rachael Wasikowski, Jeffrey B. Hodgin, Johann E. Gudjonsson, J. Michelle Kahlenberg, Deepak A. Rao

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Figure 1

Identification of T and NK cell states in lesional and nonlesional skin biopsies of cutaneous lupus patients.

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Identification of T and NK cell states in lesional and nonlesional skin ...
(A) Schematic diagram of study, including sample collection, initial scRNA-Seq, and fine clustering of T cell subsets. (B) UMAP plots of main T cell lineage marker expression. (C) Bar plot of cluster assignments for captured cells in each sample. (D) Dot plot of differentially expressed genes in each identified cluster. HD, healthy donor; CL, cutaneous lupus; L, lesional; N, nonlesional.

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