Abstract Background The small intestine harbors a rich array of intestinal intraepithelial lymphocytes (IELs) that interact with structural cells to collectively sustain gut immune homeostasis. Dysregulation of gut immune homeostasis was implicated in the pathogenesis of multiple autoimmune diseases, however, whether this homeostasis is disrupted in a lupus autoimmune background remains unclear. Methods We performed single-cell RNA sequencing (scRNA-seq) analyses to elucidate immune and structural milieu in the intestinal epithelium of MRL/Lpr lupus mice (Lpr mice) and MRL/Mpj control mice (Mpj mice). Comprehensive analyses including unsupervised clustering, trajectories, and cellular communication were performed. The primary findings from scRNA-seq were further validated by quantitative polymerase chain reaction (qPCR), flow cytometry, and in vivo experiments including selenium supplementation. Results We observed a significant reduction in CD8αα + IELs, accompanied by a marked increase in CD8αβ + IELs in Lpr mice. Additionally, subsets of CD8 + IELs exhibiting significantly enhanced effector functions were found to be markedly enriched in Lpr mice. Intercellular communication patterns within intestinal epithelial immune and structural cells were found to be specifically altered in Lpr mice. Moreover, scRNA-seq revealed significantly decreased intestinal TCRγδ T cells (γδT) associated with reduced aryl-hydrocarbon receptor repressor (AHRR) expression and subsequent oxidative stress and ferroptosis in Lpr mice. Antioxidant selenium effectively reversed the loss of γδT in Lpr mice, improved the gut barrier, and alleviated lupus symptoms. Conclusions Our high-resolution single-cell atlas enhances the understanding of the immune and structural milieu of intestinal epithelium in lupus and provides new insights into lupus pathogenesis mediated by intestinal immune dysregulation.

The dysregulated differentiation of T lymphocyte play an important role in systemic lupus erythematosus (SLE). However, the underlying mechanism remains unclear. Here, we showed that many transcripts derived from human endogenous retroviruses (HERVs) were highly expressed in CD4 + T cells from SLE patients due to DNA hypomethylation, some of which were characterized by double strand RNAs (dsRNAs). Excessive dsRNAs promoted Th1/Th17 differentiation and inhibited Treg cell differentiation via the activation of dsRNA sensor retinoic acid-inducible gene I (RIG-I). And T cell-specific ablation of RIG-I alleviated disease progression in experimental autoimmune encephalomyelitis (EAE) mice model and lupus-like mice model. Importantly, we demonstrated that dsRNA-activated RIG-I protein bind lactate dehydrogenase A (LDHA) and regulate histone lysine 18 lactylation (H3K18Lac) and acetylation (H3K18Ac) modifications in T cell differentiation via changing lactate level. Collectively, our findings uncover a novel role and mechanism of HERVs and RIG-I in regulating the aberrant differentiation of T cells in SLE patients.

International Journal of DermatologyEarly View Commentary The gut microbiota in alopecia areata: Potential predictive biomarkers and therapy targets? Zhi Hu, Zhi Hu orcid.org/0009-0005-9596-6880 Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, ChinaSearch for more papers by this authorMing Zhao, Corresponding Author Ming Zhao [email protected] Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital of Central South University, Changsha, China Correspondence Ming Zhao Hospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 China E-mail: [email protected]Search for more papers by this author Zhi Hu, Zhi Hu orcid.org/0009-0005-9596-6880 Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, ChinaSearch for more papers by this authorMing Zhao, Corresponding Author Ming Zhao [email protected] Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases, Chinese Academy of Medical Sciences, Nanjing, China Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital of Central South University, Changsha, China Correspondence Ming Zhao Hospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing 210042 China E-mail: [email protected]Search for more papers by this author First published: 08 March 2024 https://doi.org/10.1111/ijd.17123 Conflict of interest: None. Funding source: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Mahmud MR, Akter S, Tamanna SK, Mazumder L, Esti IZ, Banerjee S, et al. Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases. Gut Microbes. 2022; 14(1):2096995. 10.1080/19490976.2022.2096995 PubMedWeb of Science®Google Scholar 2Liu Z, Liu X. Gut microbiome, metabolome and alopecia areata. Front Microbiol. 2023; 14:1281660. 10.3389/fmicb.2023.1281660 PubMedWeb of Science®Google Scholar 3Xu W, Zhang L, Song X. Exploring the link between gut microbiota and alopecia areata: a two-sample Mendelian randomization analysis. Int J Dermatol. 2024. https://doi.org/10.1111/ijd.17032 10.1111/ijd.17032 PubMedWeb of Science®Google Scholar 4Galván-Peña S, Zhu Y, Hanna BS, Mathis D, Benoist C. A dynamic atlas of immunocyte migration from the gut. Sci Immunol. 2024; 9(91):eadi0672. 10.1126/sciimmunol.adi0672 CASPubMedWeb of Science®Google Scholar 5De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-skin axis: current knowledge of the interrelationship between microbial dysbiosis and skin conditions. Microorganisms. 2021; 9(2): 353. 10.3390/microorganisms9020353 CASPubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Systemic lupus erythematosus (SLE) is characterized by immune dysregulation, with neutrophil infiltration in skin lesions contributing to inflammation and disease progression. However, the interaction between fibroblasts and neutrophils in SLE skin lesions has not been fully explored. Using single-cell RNA sequencing, we identified a unique CXCL1+ fibroblast subset in SLE lesions. We found that CXCL1+ fibroblasts recruit and activate neutrophils, increasing the production of inflammatory mediators, reactive oxygen species, and neutrophil extracellular traps. These fibroblasts also facilitated the transition of neutrophils to a low-density phenotype. Notably, these fibroblasts delayed neutrophil apoptosis, extending their survival and amplifying inflammation. Serum amyloid A1, secreted by CXCL1+ fibroblasts, emerged as a key activator of neutrophils. Activated neutrophils, in turn, secreted IL-1β to induce CXCL1+ fibroblasts differentiation via activating the NF-κB pathway. In conclusion, our findings reveal that IL-1β-induced CXCL1+ fibroblasts significantly modulate pro-inflammatory neutrophils, underscoring the critical crosstalk between fibroblasts and neutrophils in SLE pathogenesis.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.

Systemic lupus erythematosus (SLE) is characterized by loss of self-tolerance and persistent self-aggression, sustained chronic inflammation, production of autoantibodies and multi-system damage, and is largely incurable to date. The gut microbiota and its metabolites, now recognized as crucial environmental triggers of local/systemic immune reactions, have been implicated in the development and progression of SLE. Fecal microbiota transplantation (FMT) is restoration of disturbed microbiota by transplanting foreign gut microbiota from healthy individuals into the gastrointestinal tract of diseased individuals. Our previous clinical trial suggests that FMT is a potentially safe and effective treatment for SLE. In order to elucidate the potential effect of FMT on peripheral immune cells of patients with SLE, we collected PBMCs (n = 30) of 13 SLE patients who participated in the clinical trial before and after the FMT-treatment, and performed single-cell RNA sequencing. The results first revealed that peripheral T lymphocytes of SLE patients decreased and NK cells increased after the FMT treatment. Then, sub-clustering analysis discovered that total CD4+ T cells highly expressed genes of IL7R, CD28, and CD8+ T cells highly expressed genes of GZMH and NKG7 after FMT treatment. Moreover, FMT treatment reduced the expression of interferon-related genes (IRGs) in CD4+ T, CD8+ T, DP, NK, and B cells of SLE patients. More importantly, interferon-related pathways were more enriched in cells of the FMT non-responder group, and further the interferon genes expression of lymphocytes and myeloid cells was negatively correlated with the efficiency of FMT treatment. Collectively, our data identified various immunophenotypic and associated gene set changes following FMT treatment, illustrating the heterogeneity of response to FMT treatment in SLE.

Abnormal macrophage polarization is generally present in autoimmune diseases. Overwhelming M1 macrophage activation promotes the continuous progression of inflammation, which is one of the reasons for the development of autoimmune diseases. However, the underlying mechanism is still unclear. Here we explore the function of Regulatory factor X1 (RFX1) in macrophage polarization by constructing colitis and lupus-like mouse models. Both in vivo and in vitro experiments confirmed that RFX1 can promote M1 and inhibit M2 macrophage polarization. Furthermore, we found that RFX1 promoted DNA demethylation of macrophage polarization-related genes by increasing APOBEC3A/Apobec3 expression. We identified a potential RFX1 inhibitor, adenosine diphosphate (ADP), providing a potential strategy for treating autoimmune diseases.

The role of gut microbiome and metabolic substances in the development of autoimmune diseases has gradually been revealed. However, the relevant gut features in pemphigus have not been well clarified. We collected stool samples from pemphigus patients and healthy controls (HCs). Metagenomic sequencing and liquid chromatography-mass spectrometry (LC/MS) metabolome sequencing were performed to analyze the compositional and metabolic alternations of the gut microbiome in pemphigus patients and HCs. We observed the reduced richness and diversity and greater heterogeneity in pemphigus patients, which was characterized by a significant decrease in Firmicutes and an increase in Proteobacteria. At the species level, Intestinal pathogenic bacteria such as Escherichia coli and Bacteroides fragilis were significantly enriched, while anti-inflammatory bacteria and butyric acid-producing bacteria were significantly reduced, which were related to clinical indicators (Dsg1/3 and PDAI). 4 species were selected by the machine learning algorithm to better distinguish pemphigus patients from healthy people. Metabolomic analysis showed that the composition of pemphigus patients was different from that of HCs. PE (18:3 (6Z,9Z, 12Z)/14:1 (9Z)) was the main metabolic substance in pemphigus and involved in a variety of metabolic pathways. While Retinol, flavonoid compounds and various amino acids decreased significantly compared with HCs. Furthermore, we found that differences in the levels of these metabolites correlated with changes in the abundance of specific species. Our study provides a comprehensive picture of gut microbiota and metabolites in pemphigus patients and suggests a potential mechanism of the aberrant gut microbiota and metabolites in the pathogenesis of pemphigus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder in which excessive CD4+ T-cell activation and imbalanced effector T-cell differentiation play critical roles. Recent studies have implied a potential association between posttranscriptional N6-methyladenosine (m6A) modification and CD4+ T-cell-mediated humoral immunity. However, how this biological process contributes to lupus is not well understood. In this work, we investigated the role of the m6A methyltransferase like 3 (METTL3) in CD4+ T-cell activation, differentiation, and SLE pathogenesis both in vitro and in vivo. The expression of METTL3 was knocked down and METTL3 enzyme activity was inhibited using siRNA and catalytic inhibitor, respectively. In vivo evaluation of METTL3 inhibition on CD4+ T-cell activation, effector T-cell differentiation, and SLE pathogenesis was achieved using a sheep red blood cell (SRBC)-immunized mouse model and a chronic graft versus host disease (cGVHD) mouse model. RNA-seq was performed to identify pathways and gene signatures targeted by METTL3. m6A RNA-immunoprecipitation qPCR was applied to confirm the m6A modification of METTL3 targets. METTL3 was defective in the CD4+ T cells of SLE patients. METTL3 expression varied following CD4+ T-cell activation and effector T-cell differentiation in vitro. Pharmacological inhibition of METTL3 promoted the activation of CD4+ T cells and influenced the differentiation of effector T cells, predominantly Treg cells, in vivo. Moreover, METTL3 inhibition increased antibody production and aggravated the lupus-like phenotype in cGVHD mice. Further investigation revealed that catalytic inhibition of METTL3 reduced Foxp3 expression by enhancing Foxp3 mRNA decay in a m6A-dependent manner, hence suppressing Treg cell differentiation. In summary, our findings demonstrated that METTL3 was required for stabilizing Foxp3 mRNA via m6A modification to maintain the Treg differentiation program. METTL3 inhibition contributed to the pathogenesis of SLE by participating in the activation of CD4+ T cells and imbalance of effector T-cell differentiation, which could serve as a potential target for therapeutic intervention in SLE.

OBJECTIVES:Three-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregulated in systemic lupus erythematosus (SLE). METHODS:We performed Hi-C experiments using CD4+ T cells from 7 patients with SLE and 5 age-matched and sex-matched healthy controls (HCs) combined with RNA sequencing analysis. Further integrative analyses, including transcription factor motif enrichment, SPI1 knockdown and histone modifications (H3K27ac, H3K4me1, H3K4me3), were performed for altered loop-associated gene loci in SLE. RESULTS:We deciphered the 3D chromosome organisation in T cells of patients with SLE and found it was clearly distinct from that of HCs and closely associated with the disease activity of SLE. Importantly, we identified loops within chromosomes associated with the disease activity of SLE and differentially expressed genes and found some key histone modifications close to these loops. Moreover, we demonstrated the contribution of the transcription factor SPI1, whose motif is located in the altered loop in SLE, to the overexpression of interferon pathway gene. In addition, we identified the potential influences of genetic variations in 3D genome alterations in SLE. CONCLUSIONS:Our results highlight the 3D genome structure alterations associated with SLE development and provide a foundation for future interrogation of the relationships between chromosome structure and gene expression control in SLE.

BACKGROUND:CD4+ T cells have a vital role in the pathogenesis of systemic lupus erythematosus (SLE), abnormal gene expression in CD4+ T cells partly accounting for dysfunctional CD4+T cells. However, the underying regulatory mechanisms of abnormal gene expression in CD4+ T cells derived from SLE patients are not fully understood.METHODS:The peripheral blood CD4+ T cells were acquired from 4 SLE patients and 4 matched healthy controls. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) was conducted to screen differentially accessible chromatin regions between SLE and normals, and motif prediction was used to identify potentially key transcription factors (TFs) involved in CD4+T dysfunction. RNA sequencing (RNA-seq) was performed to screen differentially expressed genes in SLE CD4+T cells. ATAC-seq and RNA-seq were integrated to further analyze the relationship between chromatin accessibility and gene expression. KEGG pathway enrichment analysis was to determine enriched pathways of interactions between all predicted TFs and differentially expressed genes (DEGs). Meanwhile, the expression changes of target genes followed by siRNA knockdown of the predicted TF were experimentally verified by qPCR. Finally, the H3K27ac modification levels of immune-related genes with open chromatin and up-regulated expression in SLE CD4+T cells was detected by ChIP-qPCR.RESULTS:We identified 3067 differentially accessible regions (DARs) and 1292 DEGs. TF prediction and functional enrichment analyses showed the TF-gene interaction networks were enriched predominantly in T helper 17 (Th17) cell differentiation, the cell cycle and some signaling pathways. Top 5 TFs were predicted based on overlapping genes between the DAR-related genes and the DEGs: ZNF770, THAP11, ZBTB14, ETV1, POU3F1. Validation experiments indicated that the expression of TRIM25, CD163, BST2, IFIT5, IFITM3, OASL, TBX21, IL15RA and IL12RB2 was significantly downregulated in CD4+Tcells with ZNF770 knockdown. H3K27ac showed significantly higher levels in the promoter regions of KLF4 and MX2 in SLE CD4+ T cells.CONCLUSION:These DARs associated with this disease may become targets for future treatment of SLE.

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by multiple organ damage accompanied by the over-production of autoantibodies. Decreased intestinal flora diversity and disruption of homeostasis have been proven to be associated with pathogenesis of SLE. In previous study, a clinical trial was conducted to verify the safety and effectiveness of fecal microbiota transplantation (FMT) in the treatment of SLE. To explore the mechanism of FMT in the treatment of SLE, we included 14 SLE patients participating in clinical trials, including 8 in responders group (Rs) and 6 in non-responders group (NRs), and collected peripheral blood DNA and serum. We found that the serum of S-adenosylmethionine (SAM), methylation group donor, was upregulated after FMT, accompanied by an increase in genome-wide DNA methylation level in Rs. We further showed that the methylation levels in promoter regions of Interferon-γ (IFN-γ), induced Helicase C Domain Containing Protein 1 (IFIH1), endoplasmic reticulum membrane protein complex 8 (EMC8), and Tripartite motif-containing protein 58 (TRIM58) increased after FMT treatment. On the contrary, there was no significant change in the methylation of IFIH1 promoter region in the NRs after FMT, and the methylation level of IFIH1 in the Rs was significantly higher than that in the NRs at week 0. We included 850 K methylation chip sequencing, combining previous data of metagenomic sequencing, and metabolomic sequencing for multi-omics analysis to discuss the relationship between flora-metabolite-methylation in FMT. Finally, we found that hexanoic acid treatment can up-regulate the global methylation of peripheral blood mononuclear cells in SLE patients. Overall, our results delineate changes in methylation level after FMT treatment of SLE and reveal possible mechanisms of FMT treatment in terms of the recovery of abnormal hypomethylation.

Subacute cutaneous lupus erythematosus (SCLE) is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythemas, the pathological mechanism of which is poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing (scRNA-seq) of SCLE skin lesions and integrated the scRNA-seq data from skin tissues of healthy controls (HCs). Our results identified expanded fibroblasts and keratinocytes subtypes, abnormally activated lymphocyte and inflammatory M1 macrophages in SCLE. In SCLE, stromal cells, such as keratinocytes and fibroblasts, showed enhanced chemotactic functions for recruiting immune cells. Importantly, interferon-related genes were identified as key intermediate genes in the potential trajectory of fibroblasts, keratinocytes, and B cells from HCs to SCLE. Our investigation provides a comprehensive description of cell composition in SCLE and highlights several important clues for understanding the pathogenesis of SCLE.

Skin inflammation and photosensitivity are common in lupus erythematosus (LE) patients, and ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) patients. Type I interferons (IFN) are upregulated in LE skin after UV exposure; however, the mechanisms to explain UVB-induced inflammation remain unclear. Here, we demonstrated that UVB irradiation-induced activation of human endogenous retroviruses (HERVs) plays a major role in the immune response. UVB-induced HERV-associated dsRNA transcription and subsequent activation of the innate antiviral RIG-I/MDA5/IRF7 pathway led to downstream transcription of interferon-stimulated genes, which promotes UVB-induced apoptosis and proliferation inhibition in keratinocytes through RIG-I and MDA5 pathways. Our findings indicate that UVB irradiation induces HERV-dsRNA overexpression, and the dsRNA-sensing innate immunity pathway promotes type I IFN production, which may be a potential mechanism of skin inflammatory response and skin lesion of SLE/DLE.

Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are both types of lupus, yet the characteristics, and differences between them are not fully understood. Here we show single-cell RNA sequencing data of cutaneous lesions from DLE and SLE patients and skin tissues from healthy controls (HCs). We find significantly higher proportions of T cells, B cells and NK cells in DLE than in SLE. Expanded CCL20+ keratinocyte, CXCL1+ fibroblast, ISGhiCD4/CD8 T cell, ISGhi plasma cell, pDC, and NK subclusters are identified in DLE and SLE compared to HC. In addition, we observe higher cell communication scores between cell types such as fibroblasts and macrophage/dendritic cells in cutaneous lesions of DLE and SLE compared to HC. In summary, we clarify the heterogeneous characteristics in cutaneous lesions between DLE and SLE, and discover some specific cell subtypes and ligand-receptor pairs that indicate possible therapeutic targets of lupus erythematosus.

Abstract Background The aberrant differentiation of T follicular helper (Tfh) cells plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of regulating Tfh cells differentiation remains unclear. Long noncoding RNAs (lncRNAs) act as important regulators in the processes of innate and adaptive immune response. Whether lncRNAs are involved in regulating Tfh cell differentiation and autoimmune responses need to be further identified. Methods The characters and functions of human IL21‐AS1 and its mouse homologous lncRNA (mIl21‐AS) were investigated by a series of biochemical assays and cell transfection assay. mIl21‐AS1 regulating humoral immune response in vivo was explored by keyhole limpet haemocyanin (KLH) and chronic graft versus host disease (cGVHD) model. Results Human IL21‐AS1 and its mouse homologous lncRNA (mIl21‐AS) were identified and cloned. We uncovered that IL21‐AS1 was highly expressed in CD4+ T cells of SLE patients and Tfh cells, which promoted differentiation of Tfh cells. Mechanistically, IL21‐AS1 bound heterogeneous nuclear ribonucleoprotein U and recruited acetyltransferases CREB‐binding protein to the promoter of IL21, leading to the transcriptional activation of IL21 and Tfh cells differentiation through increasing Histone H3 acetylation level on IL21 promoter. Moreover, Tfh proportion and antibodies production were significantly increased in mIl21‐AS knock‐in mice immunized with KLH. mIl21‐AS1 overexpression also exacerbated the lupus‐like phenotype in cGVHD mice model. Conclusions Our results demonstrate that IL21‐AS1 activates IL21 transcription via epigenetic mechanism to promote germinal centre response, adding insight into the molecular regulation of autoimmune pathogenesis and providing a novel target for SLE treatment.

Xuejun Zhang and colleagues report results of a genome-wide association study of systemic lupus erythematosus (SLE) in a Chinese Han population. Their work identifies nine new SLE susceptibility loci and reveals overlap in the spectrum of risk alleles shared between Chinese Han and European populations.