Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus

Zhou, Haiyan; Hu, Bailong; Huang, Niannian; Mo, Xiangang; Li, Wei; Zhang, Bei; Wei, Bo; Gao, Mingyang; Wang, Yiming; Liu, Xingde; Liao, Joshua M.

doi:10.1007/s10067-018-4124-0

Cited by 27 publications

(22 citation statements)

References 20 publications

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“…The expression of checkpoint molecules such as PD-1 and TIGIT have been reported to be dampened on immune cells in SLE patients [22, 23]. However, in our study, SLE subjects seemed to exhibit increased levels of PD-1, similar to what has been just revealed in systemic sclerosis [24] and another study showing that SLE patients exhibited increased frequencies of circulating PD1 + ICOS + T follicular helper cells and PD1 + ICOS + T memory cells [25], possibly suggesting a feedback mechanism of the immune system. These inhibitory receptors could have failed to suppress overwhelming T cell activation as a result of upregulation of other activation pathways.…”

Section: Discussionsupporting

confidence: 77%

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

Zhou

et al. 2019

Mediators of Inflammation

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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.

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Section: Discussionsupporting

confidence: 77%

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

Zhou

et al. 2019

Mediators of Inflammation

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“…Consistently, we found that Prevnar-13 was associated with increased IL-10 production by T cells which suppresses the IL-2 production required for T-cell clonal expansion (38, 39). Conversely, production of IL-4 and IL-17, two cytokines associated with active disease (40), were inhibited by Prevnar-13.…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal Polysaccharide Vaccine Ameliorates Murine Lupus

et al. 2019

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Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (TFH) and T follicular regulatory cells (TFR), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with fewer TFH and increased TFR. Together, the data support use of Prevnar vaccination in individuals with SLE.

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“…Furthermore, there is evidence suggesting an augmentation of CD4 + T EM cells population in SLE pathogenesis (44). Also, the PD1 + ICOS + T CM , and PD1 + ICOS + T EM subpopulation are increased in SLE patients and T EM positively cells correlated with the severity of the disease (45). Likewise, it has been observed an enrichment of CD4 + T EM -cell associated genes within SLE loci, Crohn's loci and RA loci (46).…”

Section: Memory T Cells: Key Player In the Pathogenesis Of Autoimmunementioning

confidence: 99%

Mesenchymal Stem Cells Improve Rheumatoid Arthritis Progression by Controlling Memory T Cell Response

et al. 2019

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In the last years, mesenchymal stem cell (MSC)-based therapies have become an interesting therapeutic opportunity for the treatment of rheumatoid arthritis (RA) due to their capacity to potently modulate the immune response. RA is a chronic autoimmune inflammatory disorder with an incompletely understood etiology. However, it has been well described that peripheral tolerance defects and the subsequent abnormal infiltration and activation of diverse immune cells into the synovial membrane, are critical for RA development and progression. Moreover, the imbalance between the immune response of pro-inflammatory and anti-inflammatory cells, in particular between memory Th17 and memory regulatory T cells (Treg), respectively, is well admitted to be associated to RA immunopathogenesis. In this context, MSCs, which are able to alter the frequency and function of memory lymphocytes including Th17, follicular helper T (Tfh) cells and gamma delta (γδ) T cells while promoting Treg cell generation, have been proposed as a candidate of choice for RA cell therapy. Indeed, given the plasticity of memory CD4 + T cells, it is reasonable to think that MSCs will restore the balance between pro-inflammatory and anti-inflammatory memory T cells populations deregulated in RA leading to prompt their therapeutic function. In the present review, we will discuss the role of memory T cells implicated in RA pathogenesis and the beneficial effects exerted by MSCs on the phenotype and functions of these immune cells abnormally regulated in RA and how this regulation could impact RA progression.

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Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus

Cited by 27 publications

References 20 publications

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

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

Pneumococcal Polysaccharide Vaccine Ameliorates Murine Lupus

Mesenchymal Stem Cells Improve Rheumatoid Arthritis Progression by Controlling Memory T Cell Response

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