Impaired function of PD-1(+) follicular regulatory T cells in systemic lupus erythematosus
CLINICAL AND EXPERIMENTAL IMMUNOLOGY(2021)
Abstract
Aberrant autoantibody production is characteristic of systemic lupus erythematosus (SLE), but follicular regulatory T (TFR) cells can potentially suppress this abnormality. We investigate functional changes in TFR cells from SLE patients. Circulating TFR cells were collected from 19 SLE patients and 14 healthy controls (HC) to compare molecular expression and in-vitro suppressive capacity of follicular helper T (TFH) cell proliferation. To reveal the stability of forkhead box protein 3 (FoxP3) in TFR, pyrosequencing of conserved non-coding sequence (CNS) 2 at the FoxP3 gene locus was performed. We then tested interleukin (IL)-2 in SLE-TFR cells to check restoration of suppressor function. Programmed cell death 1 (PD-1) expression in SLE-TFR cells was positively correlated with anti-DNA antibody levels and disease activity. These cells had impaired suppressive function for TFH cells with decreased expression of suppression mediators FoxP3, cytotoxic T lymphocyte antigen 4 (CTLA-4) and IL-2 receptor alpha (IL-2R alpha). Pyrosequencing identified hyper-methylation in CNS2 region of SLE-TFR cells comparing to HC. With in-vitro IL-2 stimulation, PD-1 expression of TFR cells significantly decreased, together with increased expression of FoxP3 and CTLA-4, especially at a low dose. Thus, SLE-TFR cells have functionally defective to TFH suppression, but low-dose IL-2 therapy might be useful to restore this ability.
MoreTranslated text
Key words
follicular regulatory T cell,FoxP3,IL-2,PD-1,systemic lupus erythematosus
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined