Open AccessTh17 and natural Treg cell population dynamics in systemic lupus erythematosus
Author(s) -
Yang Ji,
Chu Yiwei,
Yang Xue,
Gao Di,
Zhu Lubing,
Yang Xinrong,
Wan Linlin,
Li Ming
Publication year - 2009
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24499
Subject(s) - immunology , peripheral blood mononuclear cell , population , flow cytometry , medicine , cell , lupus erythematosus , interleukin 17 , cytokine , biology , in vitro , antibody , biochemistry , genetics , environmental health
Abstract Objective To investigate the relative abundance and activities of Th17 cells and natural Treg cells in systemic lupus erythematosus (SLE). Methods Blood samples were collected from 50 adult patients with SLE. Samples were processed to detect Th17 cells and natural Treg cells by flow cytometry, and related gene expression was assessed by real‐time reverse transcription–polymerase chain reaction. Skin biopsy specimens were collected for histologic assessment. The function of Th17 cells in relation to human umbilical vein endothelial cells (HUVECs) was studied in vitro. Th17 cells were also examined in lupus‐prone MRL/Mp‐ lpr/lpr (MRL/ lpr ) mice. Results We demonstrated the presence of Th17 cells among the peripheral blood mononuclear cells (PBMCs) and in the involved organs of patients with active SLE. Both the percentage of circulating Th17 cells and the ability to produce interleukin‐17A (IL‐17A) were increased in samples derived from patients with active SLE. The number of Th17 cells increased during SLE flare, especially in patients with vasculitis, and decreased following certain treatments. We observed that IL‐17A from patients with SLE could induce adhesion molecule messenger RNA expression in HUVECs and adhesion of T cells to HUVECs. An increase in the percentage of Th17 cells was correlated with natural Treg cell depletion during disease flare. Finally, expansion of the Th17 cell population was detected in MRL/ lpr mice. Conclusion SLE flare might be linked to the expansion of the Th17 cell population and the depletion of natural Treg cell subpopulations. Expansion of the Th17 cell population might be related to a distinct cytokine environment in active SLE. Th17 cells and microenvironmental IL‐17A are involved in vascular inflammation in SLE. Antagonism of Th17 cells by IL‐17A–blocking antibodies should be explored as a treatment of SLE.