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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 1

Immune cell distributions and compositions in PS and HC.

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Immune cell distributions and compositions in PS and HC.
(A and B) The S...
(A and B) The SPADE tree plots of all HC (n = 4) (A) and all PS patients (n = 4) (B) showing the different gated immune cell subpopulations. Node color and the size of each node in the tree indicate the frequency of cells. Red arrows indicate the abundant and heterogeneous pattern of CD4 TEM cells in PS. (C) Sunburst representation of the distributions and frequencies of the various cell subsets. Results are expressed as percentages. (D) Box plots comparing cell frequency (percentage of CD45+ cells) of B cells, T cells, CD4 naive T (Tnaive) cells, CD4 TEMRA cells, and CD8 TEM cells between HC and PS groups. The 5th and 95th percentile are shown in each box, and median (center line) is marked. *P < 0.05 by 2-tailed Student’s t test. PS, psoriasis; HC, healthy controls.

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