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Published on: May 31, 2021
Pathogenic role of circulating CD4+CXCR5+ cell subpopulations in patients with chronic spontaneous urticarial
Cuie Gao1, Wen-Chiech Chen2,3, Wenying Liu1
1Department of Dermatology, Southwest Hospital, Army Medical University Chongqing 400038, China.
Insights
Frequencies of circulating CD4+CXCR5+ T cells and follicular helper T (Tfh) cells are elevated in chronic spontaneous urticaria (CSU) and correlate with disease activity, suggesting their role in CSU immunopathogenesis.
Area of Science:
- Immunology
- Dermatology
- Allergy
Background:
- Circulating CD4+CXCR5+ T cells, including follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, are crucial for immune homeostasis and humoral responses.
- These cells have been implicated in the pathogenesis of various autoimmune and inflammatory diseases.
Purpose of the Study:
- To investigate the correlation between the frequencies of CD4+CXCR5+ T cells, Tfh cells, Tfr cells, and the Tfh/Tfr ratio with disease activity in chronic spontaneous urticaria (CSU).
Main Methods:
- Flow cytometry was used to analyze the frequencies of CD4+CXCR5+ T cells, Tfh cells, and Tfr cells in peripheral blood mononuclear cells (PBMCs) from CSU patients and healthy controls.
- CXCR5 expression, plasma cytokine levels (IL-4, IL-6, IL-21), and total IgE levels were measured.
- Receiver operating characteristic (ROC) curve analysis was employed to assess the correlation between cell frequencies/levels and the urticaria activity score (UAS).
Main Results:
- CSU patients exhibited elevated frequencies of CD4+CXCR5+ T cells and Tfh cells, as well as higher Tfh/Tfr ratios, compared to healthy controls.
- CXCR5 expression was significantly higher in PBMCs of CSU patients.
- Plasma IL-4 and IL-6 levels were elevated in CSU patients and positively correlated with total IgE, while IL-21 levels were lower and negatively correlated with total IgE.
- The UAS showed a positive correlation with CD4+CXCR5+ T cell frequency, Tfh cell frequency, Tfh/Tfr ratio, and total IgE levels.
Conclusions:
- Circulating CD4+CXCR5+ T cells and Tfh cells are abnormally frequent in CSU patients.
- These cell populations and their ratio are positively correlated with disease severity (UAS).
- The findings suggest a potential role for these T cell subsets in the immunopathogenesis of CSU.
Abstract:
Accumulating evidence demonstrated that circulating CD4+CXCR5+, follicular helper T (Tfh) and follicular regulatory T (Tfr) cells maintain immune homeostasis and humoral immune response and were involved in the pathogenesis of certain autoimmune/inflammatory diseases. The current study was aimed to investigate the correlation between frequencies of CD4+CXCR5+, Tfh and Tfr cells, Tfh/Tfr and the disease activity in chronic spontaneous urticaria (CSU). Frequencies of CD4+CXCR5+, Tfh and Tfh/Tfr, but not Tfr, in peripheral blood mononuclear cells (PBMCs) were elevated in patients with CSU as compared with healthy controls. No difference was observed in the frequency of these cells between different subgroups of patients based on autologous serum skin testing (ASST), skin prick testing (SPT) and the level of total IgE. The expression of CXCR5 in PBMCs was higher in CSU than in controls, both at mRNA and protein levels. Higher levels of plasma IL-4, IL-6 and total IgE were observed in CSU, with positive correlation between IL-4/IL-6 and total IgE. The IL-21 level was lower and negatively correlated with total IgE. Using receiver operating characteristic (ROC) curve, we found positive correlation between the urticaria activity score (UAS) and CD4+CXCR5+, Tfh, Tfh/Tfr and total IgE, respectively, with area under the curves (AUCs) all greater than 0.7 (P < 0.05). These results indicated that frequencies of circulating CD4+CXCR5+ cells, Tfh cells and Tfh/Tfr were abnormal and correlated positively with disease severity, suggesting the possible involvement of these cells in the immunopathogenesis of CSU.
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