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

ABSTRACT: 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.

SUBMITTER: Izati AF

PROVIDER: S-EPMC8416093 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The emerging epitranscriptome plays an essential role in autoimmune disease. As a novel mRNA modification, N4-acetylcytidine (ac4C) could promote mRNA stability and translational efficiency. However, whether epigenetic mechanisms of RNA ac4C modification are involved in systemic lupus erythematosus (SLE) remains unclear. Herein, we detected eleven modifications in CD4+ T cells of SLE patients using mass spectrometry (LC-MS/MS). Furthermore, using samples from four CD4+ T cell pools, we identified lower modification of ac4C mRNA in SLE patients as compared to that in healthy controls (HCs). Meanwhile, significantly lower mRNA acetyltransferase NAT10 expression was detected in lupus CD4+ T cells by RT-qPCR. We then illustrated the transcriptome-wide ac4C profile in CD4+ T cells of SLE patients by ac4C-RIP-Seq and found ac4C distribution in mRNA transcripts to be highly conserved and enriched in mRNA coding sequence regions. Using bioinformatics analysis, the 3879 and 4073 ac4C hyper-acetylated and hypoacetylated peaks found in SLE samples, respectively, were found to be significantly involved in SLE-related function enrichments, including multiple metabolic and transcription-related processes, ROS-induced cellular signaling, apoptosis signaling, and NF-κB signaling. Moreover, we demonstrated the ac4C-modified regulatory network of gene biological functions in lupus CD4+ T cells. Notably, we determined that the 26 upregulated genes with hyperacetylation played essential roles in autoimmune diseases and disease-related processes. Additionally, the unique ac4C-related transcripts, including USP18, GPX1, and RGL1, regulate mRNA catabolic processes and translational initiation. Our study identified novel dysregulated ac4C mRNAs associated with critical immune and inflammatory responses, that have translational potential in lupus CD4+ T cells. Hence, our findings reveal transcriptional significance and potential therapeutic targets of mRNA ac4C modifications in SLE pathogenesis.

Project description:AimTo determine periodontitis prevalence in patients with systemic lupus erythematosus (SLE) and to assess whether periodontitis in SLE patients is associated with a greater subclinical atherosclerosis.MethodsAn observational case-control study was conducted in SLE (cases) and patients without any rheumatic diseases (controls), matched for sex. Sociodemographic and cardiometabolic variables were gathered, and SLE activity was assessed through several indexes. Periodontal examination registered probing pocket depth, clinical attachment level, bleeding on probing, plaque index, and tooth loss. Subclinical atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry, homocysteine levels, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Bivariate analyses and logistic regression were used to assess the association of any of the studied variables with SLE.ResultsSeventy-one cases and 72 controls were included in the study. Thirty-nine SLE patients (54.9%) were diagnosed with periodontitis, compared with 16 controls (22.2%). High levels of PWV (≥7.7 m/s, 75th percentile) were shown by 44.3% of the cases vs. 22.4% of the controls (p = .011). Among SLE patients, those with periodontitis showed higher PWV values (8.1 ± 1.52 vs. 7.16 ± 1.11 m/s, p = .006) and higher homeostasis model assessment index (indicative of insulin resistance) (1.7 ± 0.73 vs. 2.92 ± 3.05, p = .028) compared to those with periodontal health. Logistic regression showed that waist circumference (OR 1.06, 95% CI 1.01-1.12, p = .015); ESR (OR 1.09, 95% CI 1.03-1.16, p = .003); and bleeding on probing (OR 1.1, 95% CI 1.01-1.19, p = .018) were associated with the risk of SLE.ConclusionSystemic lupus erythematosus patients showed a higher periodontitis percentage than controls. Higher PWV values were found in SLE patients with periodontitis, indicating a higher prevalence of subclinical atherosclerosis. Patients with higher gingival bleeding showed a higher risk of SLE.

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

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