Background Rheumatoid arthritis (RA) is a complex autoimmune disease with multiple etiological factors, among which aberrant memory CD4 T cells activation plays a key role in the initiation and perpetuation of the disease. SIGIRR (single immunoglobulin IL-1R-related receptor), a member of the IL-1 receptor (ILR) family, acts as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. The aim of this study was to investigate the potential roles of SIGIRR on memory CD4 T cells in RA and the underlying cellular and molecular mechanisms. Methods Single-cell transcriptomics and bulk RNA sequencing data were integrated to predict SIGIRR gene distribution on different immune cell types of human PBMCs. Flow cytometry was employed to determine the differential expression of SIGIRR on memory CD4 T cells between the healthy and RA cohorts. A Spearman correlation study was used to determine the relationship between the percentage of SIGIRR+ memory CD4 T cells and RA disease activity. An AIA mouse model (antigen-induced arthritis) and CD4 T cells transfer experiments were performed to investigate the effect of SIGIRR deficiency on the development of arthritis in vivo. Overexpression of SIGIRR in memory CD4 T cells derived from human PBMCs or mouse spleens was utilized to confirm the roles of SIGIRR in the intracellular cytokine production of memory CD4 T cells. Immunoblots and RNA interference were employed to understand the molecular mechanism by which SIGIRR regulates TNF-α production in CD4 T cells. Results SIGIRR was preferentially distributed by human memory CD4 T cells, as revealed by single-cell RNA sequencing. SIGIRR expression was substantially reduced in RA patient-derived memory CD4 T cells, which was inversely associated with RA disease activity and related to enhanced TNF-α production. SIGIRR-deficient mice were more susceptible to antigen-induced arthritis (AIA), which was attributed to unleashed TNF-α production in memory CD4 T cells, confirmed by decreased TNF-α production resulting from ectopic expression of SIGIRR. Mechanistically, SIGIRR regulates the IL-1/C/EBPβ/TNF-α signaling axis, as established by experimental evidence and cis-acting factor bioinformatics analysis. Conclusion Taken together, SIGIRR deficiency in memory CD4 T cells in RA raises the possibility that receptor induction can target key abnormalities in T cells and represents a potentially novel strategy for immunomodulatory therapy.

Rheumatoid arthritis (RA) is a complex autoimmune disease with multiple etiological factors, among which aberrant T-cell activation plays a key role in the initiation and perpetuation of the disease. The factors that trigger T cell abnormalities in these inflammatory processes are incompletely understood. SIGIRR (single immunoglobulin IL-1R-related receptor) is a member of the IL-1 receptor (ILR) family with distinct structural and functional characteristics, acting as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. Here, we identified defects in SIGIRR in activated CD4 T cells as an underlying dysregulation. SIGIRR was preferentially distributed by human memory CD4 T cells, as revealed by single-cell RNA sequencing, and its expression was substantially reduced in RA patient-derived memory CD4 T cells, which was inversely associated with RA disease activity. SIGIRR-deficient mice were more susceptible to antigen-induced arthritis (AIA) attributed to unleashed tumor necrosis factor (TNF)-α production in antigen-specific CD4 T cells. Mechanistically, SIGIRR regulates the IL-1/C/EBPβ/TNF-α signaling axis, as established by experimental evidence and cis-acting factor bioinformatics analysis. Taken together, SIGIRR deficiency in RA CD4 T cells raised the possibility that receptor interference can target key abnormalities in T cells and represents a potentially novel strategy for immunomodulatory therapy.

Background Coronary heart disease (CHD) is causing by the aberrant aggregation of immune cells in plaque. This study aimed to identify abnormal T cell subtypes and inflammatory factors in CHD patients. Methods In total, 141 patients with CHD and 46 healthy controls at the West China hospital (Chengdu, China) between June 2020 and August 2020 were enrolled in this study. Patients were divided into five groups: Healthy control, SAP, UAP, AMI, and SCHD, based on the coronary angiography score and the clinical manifestations. Patients with any one of the following diseases were excluded: tumor, severe infectious disease, and severe inflammation. T cell subsets were analyzed using flow cytometry. Plasma concentration of cytokines were analyzed by Luminex. Results Flow cytometric analysis revealed that the number of ThGM cells was higher in CHD patients. The proportion of Th17 and Th1 cells were also increased in CHD patients. levels of IL-4, IL-5, IL-6, and IL-10 were significantly higher in CHD patients (P < 0.05). However, levels of GM-CSF were slightly lower in CHD patients. The multivariate analysis included 187 participants. Of these, 46 did not develop heart failure, 17 developed SCHD, 20 developed SAP, 69 developed UAP, and 35 developed AMI. In multivariate analysis, BMI, Hyperlipaemia, Hypertension, Total cholesterol, HDL, and LDL were not associated with CHD or GM-CSF expressing cell number. Using ANOVA for CHD clinical score studies. Using the student’s t test to assess between groups. Conclusions Our results suggested that ThGM can be considered as a diagnostic marker of CDH.

Background Coronary heart disease (CHD) is causing by the aberrant aggregation of immune cells in plaque. This study aimed to identify abnormal T cell subtypes and inflammatory factors in CHD patients.Methods and results T cell subsets from 187 CHD patients were analyzed using flow cytometry. Plasma concentration of cytokines were analyzed by Luminex. Flow cytometric analysis revealed that the number of ThGM cells was higher in CHD patients. The proportion of Th17 and Th1 cells were also increased in CHD patients. levels of IL-4, IL-5, IL-6, and IL-10 were significantly higher in CHD patients (P<0.05). However, levels of GM-CSF were slightly lower in CHD patients. Conclusions ThGM can be considered as a diagnostic marker of CDH.

BackgroundIndocyanine green angiography (ICG‐A) has been widely applied for intraoperative flap assessment in DIEP flap breast reconstruction. However, the beneficial effect of ICG‐A in DIEP flap breast reconstruction is still uncertain and no standardized protocol is available. This study aims to analyze the clinical outcome and comprehensively review protocols of this field.MethodsA systematic review was conducted in MEDLINE, EMBASE, and Cochrane CENTRAL databases until September 15, 2022. Studies on the utility of intraoperative ICG‐A in DIEP breast reconstruction were included. Data reporting reconstruction outcomes were extracted for pooled analysis.ResultsA total of 22 studies were enrolled in the review, among five studies with 1021 patients included in the meta‐analysis. The protocols of ICG‐A assessment of DIEP flap varied among studies. According to the pooled results, the incidence of postoperative fat necrosis was 10.89% (50 of 459 patients) with ICG‐A and 21.53% (121 of 562 patients) with clinical judgment. The risk for postoperative fat necrosis was significantly lower in patients with intraoperative ICG‐A than without (RR 0.47 95% CI 0.29–0.78, p = .004, I2 = 51%). Reoperation occurred in 5 of 48 patients (10.42%) in the ICG‐A group and in 21 of 64 patients (32.82%) in the control group summarized from reports in two studies. The risk for reoperation was lower in the ICG‐A group than in the control group (RR 0.41 95% CI 0.18–0.93, p = .03, I2 = 0%). Other complications, including flap loss, seroma, hematoma, dehiscence, mastectomy skin necrosis, and infection, were comparable between the two groups. Heterogeneities among studies were acceptable. No significant influence of specific studies was identified in sensitivity analysis.ConclusionsICG‐A is an accurate and reliable way to identify problematic perfusion of DIEP flaps during breast reconstruction. Protocols of ICG‐A differed in current studies. Intraoperative ICG‐A significantly decreases the rate of fat necrosis and reoperation in patients undergoing DIEP breast reconstruction. The synthesized results should be interpreted sensibly due to the sample size limitation. RCTs on the outcomes and high‐quality studies for an optimized ICG‐A protocol are still needed in the future.