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Lymphocyte mass cytometry identifies a CD3–CD4+ cell subset with a potential role in psoriasis
Ruru Guo, … , Xiaoxiang Chen, Liangjing Lu
Ruru Guo, … , Xiaoxiang Chen, Liangjing Lu
Published February 12, 2019
Citation Information: JCI Insight. 2019;4(6):e125306. https://doi.org/10.1172/jci.insight.125306.
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Research Article Inflammation

Lymphocyte mass cytometry identifies a CD3–CD4+ cell subset with a potential role in psoriasis

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Abstract

Psoriasis (PS) is a systemic, immune-mediated inflammatory disorder. However, the whole lymphocyte compartment and the potential pathologies of PS have not been fully characterized. In the present study, we examined whole lymphocyte subsets and signal transduction proteins using high-dimensional single-cell mass cytometry and a bioinformatics pipeline for an in-depth characterization of the immune cell subsets and protein profiles involved in pathways in the peripheral blood of patients with PS. We identified 15 major immune cell populations in T cell lineages and characterized various CD3+CD4+ Th and CD3+CD8+ T cytotoxic cell populations simultaneously across 24 leukocyte markers and 7 proteins related to the signal transduction pathways. High-dimensional analysis identified 3 new subsets that are abundant in PS peripheral blood, resembling CD3–CD4+ lymphoid tissue inducer cells, Tc17 cells, and CD8+CXCR3+ Tregs. We confirmed the CD3–CD4+ cells, and their features and functions, in an independent PS cohort. The use of single-cell mass cytometry allows systemic-level characterization of lymphocyte subpopulations and dysregulated signaling pathways in the blood of patients with PS, identifying abnormalities of different immune cell subsets. We validated that the CD3–CD4+ cells had elevated OX40 and decreased FRA2 expression, which were positively associated with the PS area and severity index.

Authors

Ruru Guo, Ting Zhang, Xinyu Meng, Zhen Lin, Jinran Lin, Yu Gong, Xuesong Liu, Yuetian Yu, Guilin Zhao, Xianting Ding, Xiaoxiang Chen, Liangjing Lu

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Figure 4

Four suspect populations in the red dotted ellipse regions composed almost entirely of cells from PS patients were identified as a potential target of treatment.

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Four suspect populations in the red dotted ellipse regions composed almo...
(A) viSNE map of PS (n = 4) and HC (n = 4) illustrating color-coded cell populations that clustered based on cell surface marker expression. viSNE analysis identifies 4 subpopulations that appear dominantly in PS. (B) ACCENSE density map of immune cells defined in A. Subpopulations 1−23 identified as local maxima in the density map are marked. The color scale signifies cell densities of similar marker phenotypes. (C) Expression signatures of the marked subpopulations P2 in A. Bar heights indicate the median expression for each marker within the subpopulation, estimated from cells sampled close to the locations of the subpopulation peaks. The horizontal line for each marker corresponds to its median expression level across all the cells in the data set. (D) Expression signatures of CD3+CD4+cells in HC and PS. Bar heights indicate the median expression for each marker within the subpopulation.

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