CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

Shukri, Nur Diyana Mohd; Izati, Aziz Farah; Ghazali, Wan Syamimee Wan; Hussin, Che Maraina Che; Wong, Kah Keng

doi:10.3389/fimmu.2021.675250

Cited by 8 publications

(5 citation statements)

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“…Interleukin (IL) is a group of cytokines crucial in regulating immune responses such as inflammation as well as mediating immune cells growth, differentiation, activation, and migration. Imbalanced T cell subsets have been identified in SLE patients associated with SLE immunopathogenesis (1)(2)(3)(4)(5). Naïve CD4 + T helper (Th) cells differentiate on activation into various cell subsets, namely Th1, Th2, and Th17, with specific profile of cytokines production and different immunopathological implications.…”

Section: Introductionmentioning

confidence: 99%

Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

et al. 2021

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The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.

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Section: Introductionmentioning

confidence: 99%

Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

et al. 2021

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“…70 Additionally, the enhancer regulating ANKRD55 in our eGRN (chr5:56139147-56162711) was also connected to IL6ST ( Figure 7G ), a gene which has been associated with T cell function and disease activity in SLE. 71 The enhancer overlaps two AD associated peaks downregulated in most ADs we analysed ( Figure 7H ), except for peak chr5:56139295-56140114, which showed a distinct upregulation in Graves’ disease. In line with this, TF activity of HIC2 (previously identified as a transcriptional repressor 72 , and linked to enhancer chr5:56139147-56162711 in our eGRN) was increased in Graves’ disease, while being decreased in psoriasis and SLE ( Figure 7I ).…”

Section: Resultsmentioning

confidence: 86%

Section: Prioritisation and Validation Of Egrn Enhancers-gene Pairs P...mentioning

confidence: 98%

Integration of genetic and epigenetic data pinpoints autoimmune specific remodelling of enhancer landscape in CD4+ T cells

Daga,

Servaas,

Kisand

et al. 2024

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CD4+ T cells play a crucial role in adaptive immune responses and have been implicated in the pathogenesis of autoimmune diseases (ADs). Despite numerous studies, the molecular mechanisms underlying T cell dysregulation in ADs remain incompletely understood. Here, we used transcriptomic and epigenomic data from CD4+ T cells of healthy donors and patients with systemic lupus erythematosus (SLE), psoriasis, juvenile idiopathic arthritis (JIA), and Graves' disease to investigate the role of enhancers in AD pathogenesis. By generating enhancer-based gene regulatory networks (eGRNs), we identified disease-specific dysregulated pathways and potential downstream target genes of enhancers harbouring AD-associated single-nucleotide polymorphisms, which we also validated using CRISPRi in primary CD4+ T cells. Our results suggest that alterations in the regulatory landscapes of CD4+ T cells, including enhancers, contribute to the development of ADs and provide a basis for developing new therapeutic approaches.

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“…Mohd shukri et al. ( 29 ) also found a similar phenomenon in SLE patients, the level of IL-35 in SLE patients was higher than that in healthy controls, but they did not further observe whether there were differences in IL-35 levels in SLE patients with different disease states.…”

Section: Discussionmentioning

confidence: 91%

“…It is worth noting that the level of IL-35 in IMN patients is always higher than that in healthy controls, whether in remission or active period, suggesting that as an autoimmune disease, IMN patients' autoimmune response remains active, even if the disease is relieved. Mohd shukri et al (29) also found a similar phenomenon in SLE patients, the level of IL-35 in SLE patients was higher than that in healthy controls, but they did not further observe whether there were differences in IL-35 levels in SLE patients with different disease states.…”

Section: Treg Cells Directly or Indirectly Inhibit Immune Response An...mentioning

confidence: 92%

Level of interleukin-35 in patients with idiopathic membranous nephropathy and its predictive value for remission time

et al. 2022

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ObjectiveAs a member of interleukin-12 family, interleukin-35 (IL-35) plays an important regulatory role in immune response. The relationship between IL-35 and idiopathic membranous nephropathy (IMN) is still unclear, and the purpose of this study is to clarify the relationship between IL-35 and disease activity and remission of IMN.MethodsThis study was a single-center, retrospective study in which all patients were diagnosed with IMN by renal biopsy or aPLA2R titer and treated with Mahuang Fuzi and Shenzhuo Decoction (MFSD). A follow-up was conducted with the endpoint of clinical complete or partial remission (CR+PR). Levels of serum IL-35 were measured and its relationship with IMN remission were analyzed. The regulatory T cell (Treg) and inducible IL-35 producing Tregs (iTR35) in peripheral blood of IMN patients were detected by flow cytometry.ResultsA total of 76 IMN patients (age 51.95 ± 13.29) were followed-up for 18 (12, 24) months. The level of serum IL-35 in all patients increased after treatment, but the degree of increase in remission group was significantly higher than that in no remission (NR) group (117.6% vs 83.7%, P<0.01). The baseline IL-35 level in remission group was higher than that in NR group (174.87 vs.151.87 pg/ml, P=0.016). Cox regression analysis showed that baseline IL-35 level was a independent risk factor for IMN remission (HR 1.081, 95%CI 1.048-1.116, P<0.001). Patients with baseline IL-35 lower than the lower quartile (≤145.49 pg/ml) had an average remission time twice as long as those with baseline IL-35 higher than the upper quartile (> 203.05 pg/ml) (12mon vs. 24mon, P<0.01). The baseline IL-35 can predict the remission time of IMN patients with either aPLA2R positive (AUC=0.673) or negative (AUC=0.745). Analysis of 18 patients with IMN showed that IL-35 level had a higher correlation with iTR35, but not Treg (r=0.613, P<0.05).ConclusionsThe level of IL-35 in patients with IMN showed an increasing trend with the progress of treatment, and the baseline IL-35 could predict the remission time of IMN patients, including those patients with negative aPLA2R. The level of IL-35 is related to the number of iTR35 cells.

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CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

Cited by 8 publications

References 75 publications

Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

Integration of genetic and epigenetic data pinpoints autoimmune specific remodelling of enhancer landscape in CD4+ T cells

Level of interleukin-35 in patients with idiopathic membranous nephropathy and its predictive value for remission time

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