P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.

B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas.

High-risk factors for adverse pregnancy outcomes in systemic lupus erythaematosus: a retrospective study of a Chinese population.

Objective: To clarify high-risk factors for adverse pregnancy outcomes (APOs) in systemic lupus erythaematosus (SLE).

Design: A retrospective chart review study.

Setting: Data were collected in a tertiary medical centre, Shanghai, China, from November 2010 to December 2018.

Supranutritional selenium suppresses ROS-induced generation of RANKL-expressing osteoclastogenic CD4 T cells and ameliorates rheumatoid arthritis.

Objective: The benefit of Se supplementation in rheumatoid arthritis (RA) has been tested in clinical trials, but results remain inconclusive. The objective of this study was to specifically investigate the potential benefit of supranutritional Se by examining human samples from an area with supranutritional Se intake and testing a mouse model of RA.

Methods: Peripheral blood mononuclear cells (PBMCs) from RA patients ( = 57) and healthy controls (HC,  = 71) from an area of supranutritional Se intake (Enshi, Hubei, China) were analysed by flow cytometry.

Protective Role of microRNA-31 in Acetaminophen-Induced Liver Injury: A Negative Regulator of c-Jun N-Terminal Kinase (JNK) Signaling Pathway.

Background & Aims: Sustained c-Jun N-terminal kinase (JNK) activation plays a major role in drug-induced liver injury (DILI). Stress-responsive microRNA-31 (miR-31) has been implicated in regulating different cellular damage, and JNK activation could induce miR-31 expression. However, the regulatory role of miR-31 in DILI has not been studied previously.

Glutamine metabolism is essential for the production of IL-17A in γδ T cells and skin inflammation.

γδ T cell is one of the most important pathogenic immune cells in autoimmunity, especially in mucosal and epithelial diseases. Metabolism is essential for the maintenance of immune homeostasis. However, unlike αβ T cells, the metabolic regulation of γδ T cell activation still remain unclear.

Sustained low-dose interleukin-2 therapy alleviates pathogenic humoral immunity via elevating the Tfr/Tfh ratio in lupus.

Objectives: Low-dose interleukin-2 (IL-2) has shown promising clinical benefits in the treatment of systemic lupus erythematosus (SLE), but how this therapy alleviates pathogenic humoral immunity remains not well understood. The dilemma is that IL-2 can suppress both follicular helper and regulatory T (Tfh and Tfr) cells, which counteract each other in regulating autoantibody production.

Methods: Female NZB/W F1 mice received recombinant human IL-2 (3 × 10 IU/dose) in three treatment regimens: (1) short, daily for 7 days; (2) medium, daily for 14 days, and (3) long, every second day for 28 days.

Health Disparities in Rheumatic Diseases: Understanding Global Challenges in Africa, Europe, Latin America, and Asia and Proposing Strategies for Improvement.

Rheumatic diseases reach across continents with some similarities as well as unique challenges. The intersection between genetic factors, environmental exposures and socioeconomic factors, as well as challenges, with delays in access to subspecialty care and medications, manifest in different ways. By understanding both the challenges and successes in different countries, while also recognizing the significant diversity both within and across continents, unified strategies to improve rheumatic disease outcomes and decrease disparities among the most vulnerable groups can be developed and disseminated.

The metabolic hormone leptin promotes the function of T cells and supports vaccine responses.

Follicular helper T (T) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate T function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying T regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations.

Bach2 attenuates IL-2R signaling to control Treg homeostasis and Tfr development.

Differentiation and homeostasis of Foxp3 regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here, we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis. Bach2 is required for the quiescence, survival, and maintenance of resting Treg cells (rTregs).

The enrichment of neutrophil extracellular traps impair the placentas of systemic lupus erythematosus through accumulating decidual NK cells.

Despite the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), the rate of adverse pregnancy outcomes is still higher than that in the general population. In the last few years, neutrophil extracellular traps (NETs) were proven to be detrimental in both autoimmune diseases and placental injury. We investigated whether NETs could be detected in the placentas of pregnant individuals with SLE and explored the relationship between NETs and decidual natural killer cells (dNKs), which comprise the majority of immune cells at the maternal-fetal interface, using clinical samples and animal models.

Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups.

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated.

SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.

Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter.

Tofacitinib restores the balance of γδTreg/γδT17 cells in rheumatoid arthritis by inhibiting the NLRP3 inflammasome.

Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (γδTreg)/γδT17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA).

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.

Zirconia Hybrid Nanoshells for Nutrient and Toxin Detection.

Monitoring milk quality is of fundamental importance in food industry, because of the nutritional value and resulting position of milk in daily diet. The detection of small nutrients and toxins in milk is challenging, considering high sample complexity and low analyte abundance. In addition, the slow analysis and tedious sample preparation hinder the large-scale application of conventional detection techniques.

Long non-coding RNA expression profiles in neutrophils revealed potential biomarker for prediction of renal involvement in SLE patients.

Objective: The long non-coding RNA plays an important role in inflammation and autoimmune diseases. The aim of this study is to screen and identify abnormally expressed lncRNAs in peripheral blood neutrophils of SLE patients as novel biomarkers and to explore the relationship between lncRNAs levels and clinical features, disease activity and organ damage.

Methods: RNA-seq technology was used to screen differentially expressed lncRNAs in neutrophils from SLE patients and healthy donors.

Taurine Metabolism Aggravates the Progression of Lupus by Promoting the Function of Plasmacytoid Dendritic Cells.

Objective: Type I interferons (IFNs) are critical in the development of systemic lupus erythematosus (SLE). Metabolic abnormalities cause dysregulation of multiple immune cells, but the metabolic regulation of type I IFN production is not well clarified in SLE. We undertook this study to define amino acid metabolism features in SLE and to explore the function of disease-relevant metabolites in the control of plasmacytoid dendritic cell (pDC)-mediated type I IFN production and the progression of SLE.

Activating transcription factor 3 inhibits endometrial carcinoma aggressiveness via JunB suppression.

The function of activating transcription factor 3 (ATF3) in cancer is context‑dependent and its role in endometrial carcinoma (EC) is yet to be elucidated. In the present study, ATF3 was indicated to be downregulated, while one of the ATF3‑interacting proteins, JunB, was upregulated in ECs according to western blot analysis. After overexpression in ECs, ATF3 inhibited the proliferation and invasion of EC cells and enhanced apoptosis, as well as suppressed the expression of JunB.

The MicroRNA Represses Th17 Cell Pathogenicity by Targeting PTEN-Regulated Pathways.

Multiple sclerosis is a chronic autoimmune disease driven by pathogenic Th17 cells. In this study, we dissected the role of - in pathogenic Th17 cells by autoantigen-specific disease models. We first showed that was upregulated in peripheral lymphoid organs and spinal cords of mice developed autoimmune encephalomyelitis.

Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology.

Background: Lupus nephritis (LN) is one of the most severe complications of SLE patients. We aim to validate urinary ALCAM as a biomarker in predicting renal disease histpathology in a Chinese lupus cohort.

Methods: In this cross-sectional study, a total of 256 patients and controls were recruited.

Preeclampsia Risk Prediction Model for Chinese Pregnant Patients With Systemic Lupus Erythematosus.

Objective: To screen for a high risk of preeclampsia in women with systemic lupus erythematosus (SLE).

Methods: A total of 513 antenatal care records of pregnant patients with SLE were obtained, and the data were randomly assigned to either a development set (n = 342) or a validation set (n = 171). Preeclampsia predictors were identified with stepwise regression, and a coefficient B of each variable was used to establish a prediction model and risk scoring system.

Inhibition of Glycolysis in Pathogenic T17 Cells through Targeting a -c-Rel Pathway Prevents Autoimmunity.

It is well known that some pathogenic cells have enhanced glycolysis; the regulatory network leading to increased glycolysis are not well characterized. In this study, we show that CNS-infiltrated pathogenic T17 cells from diseased mice specifically upregulate glycolytic pathway genes compared with homeostatic intestinal T17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro-derived pathogenic T17 cells are highly glycolytic compared with nonpathogenic T17 cells.

PBX1 expression in uterine natural killer cells drives fetal growth.

Abundant decidual natural killer (dNK) cells at the maternal-fetal interface are important during early pregnancy. However, functional subsets of dNK cells remain poorly understood. We describe a CD49aPBX homeobox 1 (PBX1) dNK cell subset that promotes fetal development in humans and mice.

MicroRNA-148a facilitates inflammatory dendritic cell differentiation and autoimmunity by targeting MAFB.

Monocyte-derived DCs (moDCs) have been implicated in the pathogenesis of autoimmunity, but the molecular pathways determining the differentiation potential of these cells remain unclear. Here, we report that microRNA-148a (miR-148a) serves as a critical regulator for moDC differentiation. First, miR-148a deficiency impaired the moDC development in vitro and in vivo.