Background The crosstalk between macrophages and trophoblasts plays a crucial role in the development and progression of recurrent spontaneous abortion (RSA). Although M1 macrophages (M1-Mφ) are known to accumulate in RSA decidual tissues, their direct functional impact on trophoblasts remains poorly characterized. Methods We established an M1-Mφ-trophoblast coculture system to investigate this interaction. CXCL9 expression was quantified in clinical samples and cell lines using qPCR, ELISA, and immunofluorescence. The migration and invasion capacities of trophoblasts were evaluated through wound healing and Transwell assays. A series of rescue experiments were conducted to uncover the underlying mechanism. Finally, an in vivo animal model was carried out to validate the corresponding functions of the CXCL9-related axis. Results Our results revealed that M1-Mφ inhibited the migration and invasion of trophoblasts by releasing CXCL9. The expression of CXCL9 in decidual tissues was significantly increased in RSA samples compared to healthy controls. Mechanistically, CXCL9 activated the CXCR3-dependent JAK/STAT1 signaling pathway. Activated STAT1 induced transcriptional upregulation of ZEB1 via IRF1, which in turn promoted the release of CCL2 to enhance macrophage recruitment. In vivo , inhibition of CXCL9 reduced embryo resorption in LPS-induced abortion mice, attenuated macrophage infiltration, and restored trophoblast migration and invasion. Conclusion Our work identifies a novel mechanism by which M1-Mφ regulate trophoblast migration and invasion through the CXCL9/STAT1/IRF1/ZEB1 axis, which in turn leads to the release of CCL2 that promotes macrophage infiltration in RSA, highlighting a new form of crosstalk between macrophages and trophoblasts.

Alopecia areata (AA) is a non-scarring inflammatory hair loss disorder characterized by a T-cell–mediated autoimmune disease that targets the hair follicles. In particular, Natural Killer Group 2 member D (NKG2D) + CD8 + T cells have been identified as central players in its pathogenesis. Current treatment options have limited efficacy and are often associated with adverse effects and high risk of relapse upon discontinuation, highlighting the need for targeted and durable therapeutic strategies. Janus kinase (JAK) inhibitors have emerged as representative therapies; however, they are limited by a high relapse rate after treatment cessation. Recently, novel therapeutic approaches such as neutralizing antibodies targeting cytokines and chemokines, and sphingosine-1-phosphate (S1P) receptor modulators have gained attention. Various molecular markers associated with AA have been identified as potential therapeutic targets. This review provides a comprehensive overview of the roles of immune cells in AA pathogenesis and introduces emerging immunomodulatory strategies and novel therapeutic targets.

Background Autoimmune Hemolytic anemia (AIHA) a relatively uncommon form of hemolytic anemia, which is characterized by the presence of autoantibodies directed against erythrocyte surface antigens, most frequently of the IgG isotype. A positive Direct Antiglobulin Test (DAT) is a key diagnostic criterion for AIHA. However, when hemolysis involves multiple autoantibodies, the standard DAT (polyspecific, anti-IgG + C3) may fail to detect certain antibodies, potentially delaying appropriate treatment. Cases presentation We reported one patient with severe AIHA mediated by IgG and IgA autoantibodies was successfully treated with Multi-drug combination regimens. A 58-year-old female was admitted to the hospital presenting with a history of fatigue, jaundice and soy sauce-colored urine for one day. Upon admission, a complete blood count revealed a critically low hemoglobin level of 41 g/L and a life-threatening condition. Initially diagnosed with IgG-mediated AIHA via standard DAT, the patient showed suboptimal response to glucocorticoids, intravenous immunoglobulin (IVIG), and transfusion support. Subsequently, through the extended DAT (monospecific, anti-IgA, anti-IgG, anti-IgM, and anti-C3) test results, the patient was diagnosed as severe AIHA mediated by IgG and IgA. Based on extended DAT results, the treatment plan was modified to include combination therapy with dexamethasone, rituximab, cyclosporine, and bortezomib, alongside intensified plasma exchange. Conclusions The extended DAT testing is recommended for all patients with clinical and laboratory evidence of acute hemolysis. Early detection helps in avoiding further investigations and provide efficient management. Severe AIHA mediated by multiple autoantibodies requires early intensive combination therapy, including immunosuppressive agents, IVIG and plasma exchange.

Ovarian cancer (OC) remains one of the most aggressive gynecological malignancies, with a five-year survival rate below 45% despite the recent advances in the introduction of targeted therapy. Moreover, immunotherapy, such as immune checkpoint inhibitors, does not improve the survival of OC patients. Lack of sufficient knowledge in understanding the complexity of the tumor microenvironment likely confers the treatment ineffectiveness. Recently, tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) have garnered research attention as they shape the tumor immune microenvironment, which plays a crucial role in disease progression and treatment response. This article reviews the complex roles of these innate immune cells in OC progression. TAMs represent a significant component of the immune infiltrate in OC, exhibiting considerable functional plasticity and can shift between anti-tumoral (M1) and pro-tumoral (M2) phenotypes. M2-like TAMs typically predominate in the tumor microenvironment, which aids in the development of immune suppression and disease progression. They also contribute to chemoresistance and metastasis; hence, their presence in tumors is associated with a worse prognosis. TANs, like TAMs, exhibit N1/N2 polarization and influence tumor progression through the formation of neutrophil extracellular traps. Understanding the biological interactions between various immune cells and cancer cells may offer new therapeutic opportunities. This review sheds light on the dynamic ecological transformation of the OC tumor microenvironment and highlights the potential of targeting TAM/TAN-mediated processes to improve OC treatment outcomes.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory condition affecting multiple organs. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the predominant pattern of kidney involvement. Amyloid A (AA) amyloidosis is a systemic amyloidosis that develops secondary to chronic inflammation or infection, most frequently affecting the kidneys. The association between IgG4-RD and AA amyloidosis is rarely reported. Herein, we report a case of a 56-year-old Chinese man presenting with a one-year history of dizziness and fatigue. The clinical evaluation and laboratory findings showed multiple enlarged lymph nodes, elevated serum creatinine, and increased levels of IgG4 and C-reactive protein. A kidney biopsy revealed IgG4-TIN. Furthermore, patchy congophilic amyloid deposits in the interstitium and arteriolar walls were positive for AA protein by immunohistochemical staining. Subsequent cervical lymph node biopsy showed IgG4-related lymphadenopathy. With prednisone and cyclophosphamide treatment, the patient achieved complete remission of renal function and a noticeable decrease in IgG4 and C-reactive protein levels. This is the first reported case to our knowledge of IgG4-related lymphadenopathy, IgG4-TIN, concurrent with renal AA amyloidosis. Clinicians should be aware that AA amyloidosis may occur in patients with IgG4-TIN, warranting further investigation into the underlying mechanisms linking AA amyloidosis to IgG4-RD.

O- linked β-N-acetylglucosamine ( O- GlcNAc) is a reversible post translational modification (PTM) involving the attachment of β-N-acetylglucosamine to serine or threonine residues of target proteins. This modification regulates a wide range of cellular functions, including signal transduction, gene expression, protein stability, and cellular metabolism. However, the regulatory patterns of O -GlcNAc in cell death have not been thoroughly summarized or extensively discussed, and detailed mechanistic studies remain limited. This review provides an updated overview of recent advances linking O -GlcNAc with principal types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis. The occurrence of these forms of PCD plays a critical role in exacerbating immune-inflammatory diseases, neurodegenerative disorders, organ and tissue injury, cardiovascular diseases, and metabolic diseases, whereas in cancer, the induction of PCD can inhibit tumor initiation and progression. Therefore, we focus on the emerging roles of O -GlcNAc in modulating principal types of PCD in these diseases and discuss its potential as a therapeutic target.

This study aimed to investigate the profiles of myositis-specific autoantibodies (MSA) and their correlation with distinct clinical features in patients with idiopathic inflammatory myopathy (IIM) in southern China. We retrospectively analyzed the medical records of 208 IIM patients, collecting data on their demographic variables, clinical manifestations, comorbidities, and MSA test results. Of the 208 patients, 185 were positive for MSAs. 69 patients were anti-MDA5 positive, 61 patients were anti-ARS positive followed by anti-SRP (34), anti-TIF1-γ (26), anti-Mi-2β (10), anti-NXP2 (10), anti-HMGCR (9), anti-Mi-2α (6), anti-cN-1A (6), and anti-SAE1 (1). Distinct clinical phenotypes were strongly associated with specific antibodies. Anti-MDA5 positive patients had shorter disease duration, less muscle involvement, but higher rates of rash, alopecia, arthritis, fever, and ILD with poorer prognosis. Anti-ARS positive patients had longer disease duration, mechanic’s hands, arthritis, fever, and ILD, but better prognosis. Both anti-MDA5 and anti-ARS antibodies were independent risk factors for developing ILD. Anti-TIF1-γ and anti-Mi-2 were most detected in IIM patients combined with malignancies, and nasopharyngeal carcinoma was the most common malignant tumor. Furthermore, hyperlipidemia and elevated cardiac biomarkers were frequently observed, particularly in patients positive for anti-SRP. The 3-month survival rate for anti-MDA5 positive patients was 87.8%, with all deaths attributed to rapidly progressive-ILD (RP-ILD). In contrast, other antibody positive patients had a 100% survival rate. This comprehensive analysis of a southern Chinese IIM cohort underscores that MSA profiles can effectively stratify patients into clinically distinct subgroups, which is crucial for predicting specific organ involvement, prognosis, and developing tailored treatment strategies.

Introduction Type 1 diabetes mellitus (T1DM) is increasing globally and represents a significant public health concern. Periodontitis affects about 11% of the global population, particularly in its severe forms, and is 1.5 to 2 times more prevalent in individuals with poorly controlled T1DM. Both conditions are multifactorial, chronic, and inflammatory, sharing a bidirectional relationship: T1DM accelerates the onset and progression of periodontitis, while periodontal inflammation worsens glycemic control. Methods This observational case-control study included adults with T1DM and metabolically healthy controls, stratified by periodontal status: healthy, gingivitis, or periodontitis. Cytokine profiles were assessed in both saliva and gingival crevicular fluid (GCF) to characterize the oral immune response. Results Significant associations were observed between T1DM and both the extent and severity of periodontal disease. T1DM patients with gingivitis exhibited increased bleeding on probing (BOP) and probing pocket depth (PPD), with BOP remaining significantly elevated in those with periodontitis. GCF analysis revealed a dysregulated immune profile in T1DM patients, characterized by elevated IL-1 β , IL-6, IL-8 and IL-17A, and reduced levels of IL-2, IL-4, IL-12p70 and IP-10. The salivary cytokine profile generally mirrored GCF findings, with higher IL-6 and IL-8 concentrations and strong correlations with key pro-inflammatory cytokines. Discussion Salivary IL-8 emerged as the most promising biomarker for distinguishing periodontal status in T1DM patients. Overall, these findings highlight the clinical potential of salivary immune profiling as a non-invasive tool for monitoring periodontal inflammation and assessing disease activity in individuals with T1DM.

PIK3CA mutations are common oncogenic mutations in breast cancer, and abnormal activation of the PI3K/AKT/mTOR pathway is a key mechanism underlying tumorigenesis and drug resistance. Inavolisib is a selective PI3Kα inhibitor approved for the treatment of hormone receptor-positive breast cancer with PIK3CA mutations. CDK4/6 inhibitors (such as palbociclib and ribociclib) block the transition from the G1 to S phase of the cell cycle and have become standard treatment for hormone receptor-positive breast cancer. Both agents exhibit resistance issues when used as monotherapy, particularly in the context of PIK3CA mutations. Studies have shown that the combination of CDK4/6 inhibitors with PI3K inhibitors (such as inavolisib) significantly enhances antitumor efficacy. Additionally, the combination therapy effectively inhibits tumor cell proliferation and induces apoptosis. In preclinical studies, this combination strategy demonstrated significant antitumor activity in various PIK3CA-mutated xenograft models. Although clinical trials (e.g., NCT04191499) are exploring the potential of inavolisib combined with CDK4/6 inhibitors, challenges remain, including toxicity management, biomarker selection, and optimizing dosing regimens to enhance efficacy and reduce side effects. This review synthesizes preclinical and clinical evidence on the mechanistic optimization of inavolisib combined with CDK4/6 inhibitors for PIK3CA-mutated breast cancer. It covers molecular mechanisms, synergistic effects, resistance strategies, biomarkers, and future directions, with an emphasis on immunological implications. The scope is limited to HR+/HER2-negative subtypes, excluding other cancers or non-PI3K-targeted therapies, to provide a focused foundation for translational immunology in oncology.