Imbalance between Th17 and regulatory T-cells in systemic lupus erythematosus

Abstract

Impaired function of regulatory T-cells (Treg) leads to a failure in immune tolerance and triggers autoimmunity. We analyzed whether the deficiency in Treg in systemic lupus erythematosus (SLE) is accompanied by an increase in effector T-cell responses. We studied the frequencies of IL-17A (Th17) and IFNg (Th1) producing CD4 + T-cells by flow cytometric detection of intracellular cytokines in PMA/ionomycin stimulated blood lymphocytes from seven patients with active SLE, eight with SLE in remission, and 11 healthy controls. Circulating Treg were evaluated as CD4 + CD25 + lymphocytes expressing FoxP3. There was no difference in the percentage of Treg cells between the groups, but their absolute counts were decreased in active SLE (5 [1-7] cells/μL) compared to inactive SLE (11 [6][7][8][9][10][11][12][13][14][15]; p = 0.05) and healthy controls (16 [10-20]; p < 0.01). Both the frequency and numbers of Th1 cells were decreased in SLE compared to controls. No difference was observed in the number of Th17 cells, which resulted in a decreased Th1/Th17 ratio. In parallel, a higher Treg/Th17 ratio in healthy controls (2.2 [1.8-3.6]) compared to active SLE (1.1 [1.0-2.1]; p < 0.05) was observed. There was a correlation between the number of Treg cells and disease activity status (SLEDAI, r = -0.59). SLE patients in the active phase of the disease are characterized by a deficiency in Treg cells and decreased Treg/Th17 ratio. This suggests that the imbalance between major T-cells subsets might be responsible for an increased proinflammatory response in the exacerbation

Changes of memory B- and T-cell subsets in lupus nephritis patients

“…In SLE this phenomenon may be associated with impaired immunosuppression, due to persistently lower numbers of regulatory T-cells or their impaired function [36,37]. Similarly to previous report [38], we observed lower frequency of naïve CD4+ T-cells and increased percentage of T EM fraction in both active-and inactive-LN.…”

Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity

“…TH17 cells secrete a profile of potent proinflammatory cytokines, including IL-17, IL-21, IL-22 and potent TNF-a and IL-6 upon certain stimulation [11]. Recent studies indicated that IL-17 aids in coordinating tissue inflammation [10][11][12]. It has been hypothesized that TH17-cells, in particular, play a pivotal role in the initiation and development of autoimmunity.…”

“…At present, human Treg cells can be characterized by a CD4 + CD25 + and transcription factor forkhead box P3 (FoxP3+) phenotype (CD4 + CD25 + FoxP3+). A decreased frequency and/or an impaired function of these cells might be involved in the development of autoimmune diseases [10,14]. Though the concept of the preventive role of Treg cells in autoimmunity is widely accepted, data regarding SLE are inconsistent [10,15].…”

“…However, human TH1 and TH2 subsets are usually defined according to IFN-c/IL-4 production because the synthesis of IL-2, IL-6, and IL-10 is not stringently restricted to a single subset [9]. In addition to well characterized TH1 and TH2 lymphocytes, naive CD4 + T-cells can be differentiated into TH17, a distinct subset of TH cells characterized by expression of the transcription factor (related orphan receptor gamma; RORct) [10]. TH17 cells secrete a profile of potent proinflammatory cytokines, including IL-17, IL-21, IL-22 and potent TNF-a and IL-6 upon certain stimulation [11].…”

Imbalance of different types of CD4+forkhead box protein 3 (FoxP3)+ T cells in patients with new-onset systemic lupus erythematosus

“…Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by high levels of serum autoantibodies against different components of cells, leading to systemic tissue and organ damage [1]. However, the aetiology and pathogenic processes of SLE are still not fully understood.…”