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Regulation of the Function of T Follicular Helper Cells and B Cells in Type 1 Diabetes Mellitus by the OX40/OX40L Axis
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Regulation of the Function of T Follicular Helper Cells and B Cells in Type 1 Diabetes Mellitus by the OX40/OX40L Axis
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Journal Article
Regulation of the Function of T Follicular Helper Cells and B Cells in Type 1 Diabetes Mellitus by the OX40/OX40L Axis
2024
Overview
Abstract
Objective/Main Outcome
To study the expression of OX40 on T follicular helper (Tfh) cells and the ligand OX40L on antigen-presenting cells (APCs) in peripheral blood of patients with type 1 diabetes mellitus (T1DM) and the role of OX40 signaling in promoting Tfh cells to assist B-cell differentiation.
Design
Cross-sectional study.
Setting
Endocrinology department of a university hospital.
Participants
Twenty-five patients with T1DM and 35 with newly diagnosed type 2 diabetes mellitus (T2DM) from January 2021 to December 2021 (39 males, 21 females; mean age: 31.0 ± 4.5, range: 19-46 years).
Interventions
None.
Methods
The peripheral blood proportion of CD4+CD25−CD127+CXCR5+PD1+ Tfh cells in patients with T1DM or T2DM and the OX40L expression in CD14+ monocytes and CD19+ B cells were analyzed by flow cytometry. The OX40 signal effect on Tfh-cell function was analyzed by coincubating B cells with Tfh cells under different conditions. Flow cytometry detected the ratio of CD19−CD138+ plasmacytes.
Results
The Tfh cells ratio and intracellular IL-21 expression in peripheral blood was significantly higher in patients with T1DM than with T2DM, and the OX40 expression in peripheral Tfh cells and OX40L expression in APC were significantly higher in T1DM. After adding OX40L protein, the CD19−CD138+-plasmacytes percentage was significantly increased and higher in T1DM. Blocking of anti-OX40L monoclonal antibodies significantly reduced the plasmacytes ratio.
Conclusion
The peripheral Tfh cells proportion increased and the OX40 expression in peripheral Tfh cells was upregulated in patients with T1DM vs patients with T2DM. OX40/OX40L signaling enhanced the Tfh-cell function to assist B-cell differentiation, which may contribute to the pathogenesis of T1DM.
Publisher
Oxford University Press
Subject
/ B cells
/ Cellular signal transduction
/ Clinical
/ Diabetes
/ Diabetes mellitus (insulin dependent)
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 1 - immunology
/ Diabetes Mellitus, Type 1 - metabolism
/ Diabetes Mellitus, Type 2 - immunology
/ Diabetes Mellitus, Type 2 - metabolism
/ Female
/ Humans
/ Male
/ Receptors, OX40 - metabolism
/ T cells
/ T Follicular Helper Cells - immunology
