Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress and status of traditional and emerging treatment strategies for SLE. Traditional treatment strategies for SLE have mainly employed non-specific approaches, including cytotoxic and immunosuppressive drugs, antimalarials, glucocorticoids, and NSAIDs. These strategies are effective in mitigating the effects of the disease, but they are not a complete cure and are often accompanied by adverse reactions. Emerging targeted therapeutic drugs, on the other hand, aim to control and treat SLE by targeting B and T cells, inhibiting their activation and function, as well as the abnormal activation of the immune system. A deeper understanding of the pathogenesis of SLE and the exploration of new targeted treatment strategies are essential to advance the treatment of this complex autoimmune disease.

The ubiquitination-dependent processing of NF-κB2 (also known as p100) is a critical step in the activation of the noncanonical NF-κB pathway. We investigated the molecular mechanisms regulating this process and showed that TRIM55 was the E3 ubiquitin ligase that mediated the ubiquitination of p100 and coordinated its processing. TRIM55 deficiency impaired noncanonical NF-κB activation and B cell function. Mice with a B cell–specific Trim55 deficiency exhibited reduced germinal center formation and antibody production. These mice showed less severe symptoms than those of control mice upon the induction of a systemic lupus–like disease, suggesting B cell–intrinsic functions of TRIM55 in humoral immune responses and autoimmunity. Mechanistically, the ubiquitination of p100 mediated by TRIM55 was crucial for p100 processing by VCP, an ATPase that mediates ubiquitin-dependent protein degradation by the proteasome. Furthermore, we found that TRIM55 facilitated the interaction between TRIM21 and VCP as well as TRIM21-mediated K63-ubiquitination of VCP, both of which were indispensable for the formation of the VCP-UFD1-NPL4 complex and p100 processing. Together, our results reveal a mechanism by which TRIM55 fine-tunes p100 processing and regulates B cell–dependent immune responses in vivo, highlighting TRIM55 as a potential therapeutic target for lupus-like disease.

T cells play critical role in multiple immune processes including antigen response, tumor immunity, inflammation, self-tolerance maintenance and autoimmune diseases et. Fetal liver or bone marrow-derived thymus-seeding progenitors (TSPs) settle in thymus and undergo T cell-lineage commitment, proliferation, T cell receptor (TCR) rearrangement, and thymic selections driven by microenvironment composed of thymic epithelial cells (TEC), dendritic cells (DC), macrophage and B cells, thus generating T cells with diverse TCR repertoire immunocompetent but not self-reactive. Additionally, some self-reactive thymocytes give rise to Treg with the help of TEC and DC, serving for immune tolerance. The sequential proliferation, cell fate decision, and selection during T cell development and self-tolerance establishment are tightly regulated to ensure the proper immune response without autoimmune reaction. There are remarkable progresses in understanding of the regulatory mechanisms regarding ubiquitination in T cell development and the establishment of self-tolerance in the past few years, which holds great potential for further therapeutic interventions in immune-related diseases.

Low-grade glioma (LGG) is heterogeneous at biological and transcriptomic levels, and it is still controversial for the definition and typing of LGG. Therefore, there is an urgent need for specific and practical molecular signatures for accurate diagnosis, individualized therapy, and prognostic evaluation of LGG. Cell death is essential for maintaining homeostasis, developing and preventing hyperproliferative malignancies. Based on diverse programmed cell death (PCD) related genes and prognostic characteristics of LGG, this study constructed a model to explore the mechanism and treatment strategies for LGG cell metastasis and invasion. We screened 1161 genes associated with PCD and divided 512 LGG samples into C1 and C2 subtypes by consistent cluster analysis. We analyzed the two subtypes' differentially expressed genes (DEGs) and performed functional enrichment analysis. Using R packages such as ESTIMATE, CIBERSOTR, and MCPcounter, we assessed immune cell scores for both subtypes. Compared with C1, the C2 subtype has a poor prognosis and a higher immune score, and patients in the C2 subtype are more strongly associated with tumor progression. LASSO and COX regression analysis screened four characteristic genes (CLU, FHL3, GIMAP2, and HVCN1). Using data sets from different platforms to validate the four-gene feature, we found that the expression and prognostic correlation of the four-gene feature had a high degree of stability, showing stable predictive effects. Besides, we found downregulation of CLU, FHL3, and GIMAP2 significantly impairs the growth, migration, and invasive potential of LGG cells. Take together, the four-gene feature constructed based on PCD-related genes provides valuable information for further study of the pathogenesis and clinical treatment of LGG.

Osteoarthritis (OA) is a common joint disease characterized by degenerative lesions of articular cartilage, subchondral osteosclerosis, osteophyte formation, and synovial inflammation. The traditional view is that OA is a degenerative disease, mainly related to mechanical damage to articular cartilage caused by age, obesity, trauma and other factors. However, in recent years, increasingly more studies have shown that immunoinflammatory responses play a crucial role in the occurrence and development of OA. There are a variety of immune cell infiltration in the joint cavity of OA, and numerous inflammatory factors are released, forming a chronic low‐grade inflammatory microenvironment, promoting articular cartilage degradation and synovial inflammation, and ultimately leading to the occurrence and development of OA. This article reviews the latest research progress on immuno‐inflammatory mechanisms such as immune cell infiltration and inflammatory factor release in OA, and discusses potential strategies for targeted immune response therapy for OA, to provide new ideas for the prevention and treatment of OA.

Introduction: Fatty acid metabolism (FAM) is essential for cancer cell proliferation and progression, contributing to membrane synthesis, energy storage, and signaling molecule production. However, effective therapeutic strategies targeting FAM are yet to be established in clinical practice. This study aimed to develop a novel FAM-related prognostic signature for bladder cancer (BLCA) and investigate its biological and clinical significance. Methods: We analyzed 359 BLCA samples and constructed a four-gene FAM-RiskScore (FAMR) signature based on FAM-related genes. Unsupervised clustering was performed to classify BLCA into molecular subtypes. The FAMR model was validated using internal and external cohorts. Functional enrichment, immune infiltration, and single-cell RNA sequencing analyses were conducted to explore underlying biological mechanisms. In vitro experiments, including proliferation and migration assays, were performed in T24 and 5637 bladder cancer cells following MAOA knockdown. Results: BLCA samples were classified into two subtypes (C1 and C2), with C1 showing better overall survival, enhanced steroid metabolism, downregulated chemokine signaling, and lower immune scores. The FAMR signature comprising PATZ1, TTC6, AEBP1, and MAOA was established. High FAMR scores–associated with low PATZ1, TTC6, MAOA, and high AEBP1 expression–predicted poor prognosis. FAMR positively correlated with pathways related to chemotaxis, inflammation, and cytoskeleton regulation, but negatively with fatty acid metabolism pathways. Higher FAMR scores were observed in females, patients aged >60, and advanced-stage tumors. Single-cell analysis revealed AEBP1 was mainly expressed in cancer-associated fibroblasts, while MAOA was enriched in cancer cells. Functional studies demonstrated that MAOA knockdown significantly enhanced proliferation and migration of bladder cancer cells in vitro. Discussion: We developed and validated a novel FAM-related risk signature that effectively predicts prognosis in BLCA. Our findings highlight MAOA as a potential tumor suppressor in bladder cancer, warranting further investigation as a therapeutic target. This FAMR model may facilitate risk stratification and inform personalized treatment strategies for bladder cancer patients.