Dysregulated T Cell Activation and Aberrant Cytokine Expression Profile in Systemic Lupus Erythematosus

Abstract

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P<0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r=0.15, P<0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown

“…Its expression on T cells was proven to correlate with lupus activity either when analyzed on CD3 + T cells (47), CD4 + T cells (22, 48–52), or CD8 + T cells (22, 49, 51, 52). It was shown that HLA-DR expression on CD3 + T cells was higher in lupus patients with anti-DNA antibodies as compared to HC (47) and was higher on CD8 + T cells in patients experiencing a lupus flare (22). Similar observations were made in patients with rheumatoid arthritis (21, 53), antiphospholipid syndrome (54) and with rejection in solid organ transplantation (55).…”

Immunology of IL-12: An update on functional activities and implications for disease

“…Several studies demonstrated that IL-12 levels are increased in SLE patients (Uzrail et al, 2019[ 190 ]; Zhou et al, 2019[ 222 ]; Guimarães et al, 2017[ 72 ]) and that risk loci for IL12RB (You et al, 2015[ 215 ]) and genetic variants of IL12B (Paradowska-Gorycka et al, 2016[ 149 ]) are associated with SLE. On the other hand, however, it has been shown that there is a T H 17/T reg imbalance in patients with SLE (Talaat et al, 2015[ 179 ]) as well as a shift in the T H 1/T H 2 balance towards T H 2 cytokines (Uzrail et al, 2019[ 190 ]), suggesting that IL-12 is one cytokine among others in disease pathogenesis.…”

Pathological mechanisms of abnormal iron metabolism and mitochondrial dysfunction in systemic lupus erythematosus

“…The principal underlying pathways involved in the pathogenesis are not fully understood but are believed to involve both the innate and adaptive immune response [ 10 ]. A loss of self-tolerance is widely believed to result in the formation of pathogenic autoreactive B and T-cells that in turn result in tissue damage [ 11 , 12 ]. The precise mechanism through which this occurs is not known, however, it is felt to involve a combination of genetic factors [ 13 ], environmental triggers [such as ultraviolet radiation and possible viral exposure] [ 14 ] and, given the marked female predominance of the disease, the influences of hormones [ 15 ].…”