Critical Reviews in Immunology最新文献

T and NK cell lymphoma with abnormal CD20 expression is a condition that primarily seen in Asians. Due to the variable expression of CD20, it is difficult to generalize its origin, leading to controversial conclusions about the role of CD20. In this review, we provide an overview of CD20 localization and function in three cell types. In NK/T-cell lymphoma (NKTCL), CD20 was discovered to be confined to B cells, presenting a mature active phenotype and having an inert course. However, in T-cell lymphoma (TCL), variable expression of CD20 antigen on T cells and NK cells correlates with tumor transformation and rituximab efficacy. We highlight the fact that CD20 expression is stage-specific and further classify CD20 antigen assignment, which contributes to understanding the variety of outcome and the function of CD20 during various phases of tumor development.

Epithelial ovarian carcinoma (EOC) is a highly lethal gynecological malignancy with limited treatment options. This study aimed to explore the regulatory roles of IRE1α and YAP1 in EOC progression and identify potential therapeutic targets. Blood and tissue samples were collected from 26 EOC patients and 10 patients with ovarian cysts. The expression of inflammatory factors in the blood was measured using ELISA. The proliferation, migration, invasion, and cell cycle of human ovarian cancer cell lines SK-OV-3, SW626, and Anglene were evaluated using MTT assays, scratch tests, Transwell assays, and flow cytometry. The effects of IRE1α inhibition on EOC cell proliferation, migration, and apoptosis were investigated using pharmacological inhibitors and shRNA knockdown. IRE1α was highly expressed in EOC patients and was negatively correlated with patient survival rates. Additionally, IRE1α scores in EOC patients were positively correlated with serum levels of TNF-α and VEGF-a. Compared to normal controls, significantly higher expressions of IRE1α and XBP1 were observed in ovarian cancer tissues and cells. Knockdown of IRE1α in ovarian cancer cells led to a significant reduction in the expression of IRE1α and XBP1s, as well as inhibited cell proliferation and survival. The IRE1α inhibitors STF-083100 and 4μ8C suppressed the proliferation, invasion, and migration of SK-OV-3 cells and reduced the expression levels of related factors. 4μ8C inhibited the degradation of YAP within SK-OV-3 cells while downregulating the expression of Cyclin D1 protein. Compared to the group treated with 4μ8C alone, the combined intervention of 4μ8C and a YAP inhibitor showed a more pronounced inhibitory effect on the proliferation of SK-OV-3 cells.This study first reveals that the IRE1α/YAP signal drives the malignant progression of EOC through the regulation of cell proliferation, migration, and invasion. The dual-targeted synergistic inhibition of IRE1α/YAP1 offers an innovative therapeutic paradigm for the treatment of EOC.

Objective: This study investigates the causal relationship between circulating inflammatory proteins and cervical cancer risk in European and Asian populations using Mendelian randomization (MR), providing insights into inflammation's role in cervical cancer pathogenesis.

Method: Data from 91 circulating inflammatory proteins from 11 cohorts (14,824 European participants, 909 cervical cancer cases, 238,249 controls; 605 cases, 89,731 controls in the Asian cohort) were analyzed. Inverse variance weighted (IVW) and MR-Egger methods were used to explore causal relationships. Sensitivity analyses, including Cochran's Q tests and leave-one-out analysis, ensured result reliability.

Results: In the European population, higher levels of CCL19, IL-1α, and IL-12B were associated with increased cervical cancer risk, while LIFR and PD-L1 were protective. In the Asian population, elevated CCL19, IL-1α, SLAM, and IL-10Rβ increased risk, while CXCL11, SULT1A1, and CXCL1 showed protective effects. Sensitivity analyses confirmed the robustness of these findings.

Conclusion: This study demonstrates a causal relationship between circulating inflammatory proteins and cervical cancer risk in both European and Asian populations. The findings highlight both pro-cancer and protective roles of specific inflammatory proteins, offering insights for biomarkers in cervical cancer risk assessment and prevention strategies.

Rheumatoid arthritis (RA) is a chronic autoimmune condition that impacts the immune system, especially through changes in the splenic immune cell system. This review provides an overview of the role of splenocytes in T cell signaling and their immune response in RA patients. The spleen acts as a critical site for the activation and differentiation of splenic immune cells like T cells, B cells, macrophages, dendritic cells, and NK cells. In RA, splenomegaly is characterized by increased immune cell infiltration and altered architecture is often observed, contributing to the disease's pathogenesis. Antigen presentation via major histocompatibility complex (MHC) molecules, specifically HLA DRB1, mediates the contact between splenocytes and T cells, resulting in the clonal growth of autoreactive T cells. This study explains how splenocytes, in response to a pro-inflammatory cytokine, affect T cell development into pathogenic subsets including Th1, Th2, and Th17. It also emphasizes how important dendritic cells and macrophages are for digesting antigens and priming T cells and how NK cells influence T cell responses by releasing cytokines. This study highlights the role of the spleen in the immunopathology of RA and offers possible treatment approaches that target immune response modulation and systemic inflammation reduction.

The relationship between human papillomavirus (HPV) and immune cells is vital for understanding the pathophysiology of infection and its role in neoplastic progression. High-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer (CC). Thus, the association between immune response cells, the virus, and its behavior according to cervical disease development could provide new ways for understanding the entire process. Since the role and the presence of the immune response cells in the uterus cervix considering HPV infection has not been elucidated so far, this study aimed to identify the immune cells involved in high-grade intraepithelial lesions (HSIL) and CC development related to uterine cervical infection caused by HR-HPV. The study population included women who had positive molecular tests for HPV. Through the databases MEDLINE, EMBASE, LILACS, Cochrane, Scopus, Web of Science, CINAHL, Science Direct, and Google Scholar we identified 6,698 studies at the beginning. After the systematic review steps, the final number of included studies was 22. Cervical lesions were distributed according to the severity of lesions in HSIL, low-grade squamous intraepithelial lesions (LSIL), and negative for intraepithelial lesions or malignancy (NILM). The cellular phenotypes presented in these publications were T lymphocytes (LT), regulatory T lymphocytes (Tregs), macrophages (MØ), natural killer cells (NK), natural killer T cells (NKT), Langerhans cells (LC), and dendritic cells (DC). Among the observed associations with cervical lesions and HR-HPV, we highlight the DC/LC and MØ being 36.4% of the cell types, followed by Tregs (31.8%) and LT CD4 / CD8 with 27.3%. The increased findings in innate and adaptive immunological response may imply both are acting together, with the innate response cells and Tregs being the most prominent. Since these cells have great importance in the maintenance and balance of the immunological system, the present study highlights the essential role of MØ and Treg cells in the process of cervical lesion severity associated with HPV, suggesting that they may be focused as prognostic markers and immunotherapeutic targets.

The MBL-associated protein of 44 kilodaltons (MAp44) belongs to the MBL-associated serine proteases (MASP) family, which is important in regulating the complement system's alternative pathway. MAp44 has been discovered to interact with complement components in numerous autoimmune illnesses leading to complement dysregulation and amplification of inflammatory reactions. These findings imply that MAp44 could be a biomarker for disease conditions and a therapeutic target for reducing complement-mediated illness. Furthermore, recent findings reveal that MAp44 has a role in cancer genesis and progression. Its participation in tumor immune evasion, angiogenesis, and metastasis has been revealed in studies, underlining its potential as a prognostic marker and a prospective target for cancer treatment. MAp44 targeting may boost immune surveillance, decrease tumor development, and improve patient outcomes in a variety of cancers. Recent research has revealed its participation in a variety of disease processes, indicating it as a possible contributor to disease etiology. The developing understanding of MAp44's role lays the groundwork for future study and development of targeted treatment approaches. Understanding the complicated processes behind its participation in autoimmune illnesses, cancer, and cardiovascular diseases opens up new possibilities for diagnosis, prognosis, and therapy approaches. Exploiting MAp44's therapeutic potential might open the door for innovative therapies targeted at improving patient outcomes in a variety of illnesses. This review gives a comprehensive knowledge of the role of MAp44 in diseases and its therapeutic potential.

Nasopharyngeal carcinoma (NPC), a malignant tumor originating from the epithelium and glands. MicroRNAs (miRNAs) play an essential role in the tumorigenesis and metastasis of NPC. They are effective biomarkers in the detection of malignant progression of NPC. In this study, we analyzed the expression profiles of miRNAs in NPC patients with Gene Expression Omnibus (GEO) database. ceRNA networks of NPC were constructed and target miRNAs were screened. MTT, colony formation and Transwell experiments were used to explore the effects of miR-205-5p on the proliferation, migration and invasion ability of NPC cells. Bioinformatics analysis combined with Double luciferase experiment verified the binding relationship between miR-205-5p and CALM1. We identified 34 long non-coding RNAs (lncRNAs), 22 miRNAs, and 145 messenger RNAs (mRNAs) and constructed a competing endogenous RNAs (ceRNA) network to explain the relationship between RNA expression profiles and NPC progression. Of which, we found that 5 miRNAs (hsa-let-7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-143-3p and hsa-miR-205-5p) are related to clinical features. We further found that miR-205-5p was highly expressed in NPC cell lines. In addition, MTT, colony formation and Transwell assays showed that miR-205-5p promoted the proliferation, migration and invasion of NPC cells. Double luciferase detection showed that miR-205-5p could target combined with CALM1. In addition, we found that miR-205-5p could promote the proliferation, migration and invasion of NPC cells by inhibited the expression of CALM1. Overall, the present study demonstrated that as a carcinogenic factor, miR-205-5p can affect the malignant progression of NPC by mediating CALM1.

Exosomes (EXOs), released by diverse cells are implicated in modulating ferroptosis under orthopedic conditions. However, the possible effects of EXOs in osteoclasts and the interaction mechanisms with ferroptosis remain poorly defined. The EXOs were isolated and identified from skeletal muscle microvascular endothelial cells (MMECs). Osteoclasts was generated using RAW264.7 cells stimulated by receptor activator of nuclear factor kappa B ligand (RANKL), followed by EXO treatment. The effects of EXOs and USP13 overexpression during osteoclastogenesis and on osteoclasts ferroptosis were determined. EXO treatment declined the tartrate-resistant acid phosphatase (TRAP)-positive numbers and osteoclast-specific genes expression in RANKL-stimulated RAW264.7 cells. Furthermore, elevated ferrous iron, malondialdehyde (MDA), lactate dehydrogenase (LDH), and reactive oxygen species (ROS) level, downregulated nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4) expression were found in response to RANKL, which were restricted after EXO treatment. Mechanistically, USP13 was carried out by EXOs and transferred to osteoclasts. USP13 overexpression exerted the suppressive role of RANKL stimulation on osteoclastogenesis and ferroptosis critical hallmarks, while augmented the activation of NRF2/GPX4 pathway. Our research revealed that MMECs-derived exosomal USP13 exhibited the anti-osteoclastogenesis effects by regulating ferroptosis. This may be a useful therapeutic target for the prevention and treatment of osteolytic diseases.

Caseinolytic protease P (ClpP) is a highly conserved serine protease that plays a pivotal role in protein homeostasis and quality control in bacteria, mitochondria of mammalian cells, and plant chloroplasts. As the proteolytic core of the ATP-dependent Clp protease complex, ClpP partners with regulatory ATPases (e.g., ClpX, ClpA) to degrade misfolded, damaged, or regulatory proteins. In bacteria, ClpP is crucial for survival under host-imposed stresses and modulates virulence through degradation of transcriptional regulators and signaling proteins, contributing to immune evasion, dormancy, and persistence. Particularly in pathogens like Mycobacterium tuberculosis, Staphylococcus aureus, and Listeria monocytogenes, ClpP supports intracellular adaptation and resistance, making it a promising target against antimicrobial-resistant (AMR) infections. In mammalian cells, mitochondrial ClpP ensures oxidative phosphorylation efficiency and regulates innate immunity. Loss of ClpP function can result in mitochondrial dysfunction, triggering immune activation via cytosolic leakage of mitochondrial DNA and subsequent cGAS-STING pathway stimulation. ClpP also influences cytokine production and immune cell differentiation. This dual role of ClpP in pathogen virulence and host immune modulation highlights its potential as an immunotherapeutic target. Pharmacological manipulation of ClpP activity offers novel opportunities for treating infectious diseases, inflammatory conditions, and cancer. Further investigation into ClpP's regulatory mechanisms could inform next-generation host-pathogen intervention strategies.

Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemical (IHC) staining were used to assess the expression of NLRC3 in tissues and cells. The effects of NLRC3 on the proliferation, apoptosis, migration, and invasion of endometrial cells were investigated via Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, cell scratch and transwell assays, respectively. The mouse model of adenomyosis was constructed. The regulation mechanisms by which NLRC3 acts were further verified in vivo study. The study revealed epithelial-mesenchymal transition (EMT) related protein expression was upregulated and NLRC3 was downregulated in endometria of patients with adenomyosis. Upregulation of NLRC3 expression reduced endometrial cell growth, migration, invasion, and promoted cell apoptosis rate. Mechanistically, upregulation of NLRC3 expression inhibited the level of EMT and blocked the PI3K/AKT/mTOR pathway activation in endometrial cells. In vivo, increased the expression of NLRC3 decreased the levels of cytokines (IL-6 and IL-8), inhibited the levels of PI3K/AKT/mTOR pathway related genes and mitigated disease severity. Our findings indicate that NLRC3 inhibits migration and invasion of adenomyosis by modulating PI3K/AKT/mTOR pathway in endometrial cells. Consequently, NLRC3 holds promise as a potential therapeutic target for adenomyosis management.