Immunological Investigations最新文献

Introduction: Endometriosis is a chronic inflammatory disease characterized by endometrial-like tissue outside the uterus. Molecules linked to natural killer (NK) and cytotoxic T cells, including granulysin (GNLY), MHC class I-related chain A (MICA), and perforin (PRF1) support immune surveillance, though their roles in endometriosis remain unclear. This study investigates the association of these molecules with clinical parameters in infertile women with endometriosis.

Methods: Eighty-seven infertile women undergoing diagnostic laparoscopy were included: 44 with endometriosis and 43 with benign gynecologic disorders. Serum and peritoneal molecules were measured using ELISA. Statistical analyses compared groups and correlated immune markers with clinical parameters.

Results: Endometriosis patients displayed significantly higher PRF1 levels in serum (p = .038) and peritoneal fluid (p = .002), particularly in late-stage disease. Serum and peritoneal PRF1 levels correlated positively with the rASRM adhesion scores. Elevated serum PRF1 was observed in ovarian endometrioma (p = .021). Peritoneal MICA was higher in late-stage endometriosis (p = .013). Serum MICA was elevated in the follicular phase compared to the luteal phase (p = .008).

Conclusion: Elevated PRF1 and MICA levels were associated with endometriosis severity, indicating their potential as biomarkers. Future studies should validate this finding and explore its therapeutic role in endometriosis.

Objective: To investigate the mechanism of serum exosomes in chronic obstructive pulmonary disease (COPD), especially the effect of lncRNA TBX2-AS1 on macrophage polarization.

Methods: Screen differentially expressed genes through bioinformatics analysis, detect the expression of related molecules in clinical samples and cell experiments, construct a mouse model and conduct functional rescue experiments, using various experimental techniques such as RT - qPCR, Western Blot, flow cytometry, ELISA, and luciferase reporter assay.

Results: TBX2-AS1 is highly expressed in the serum and serum exosomes of COPD patients, and it can promote macrophage M1 polarization and inhibit M2 polarization; it exerts its role by negatively regulating the miR-423-5p/miR-23b - 3p axis, where miR-423-5p inhibits CELSR2 expression to prevent M1 polarization, and miR-23b-3p inhibits NEK6 expression to promote M2 polarization; in vivo experiments, down-regulation of CELSR2/NEK6 can reverse the promoting effect of COPD serum exosomes on lung injury and inflammation.

Conclusion: COPD serum exosomes deliver TBX2-AS1 to macrophages, regulate the miR-423-5p-CELSR2/miR-23b-3p-NEK6 pathway, affect macrophage polarization, and exacerbate the progression of COPD, providing new directions and potential targets for the diagnosis and treatment of COPD.

Background: MicroRNAs have gained attention as key immunomodulators, with miR-155 specifically shown in various studies to drive macrophage polarization toward the classical phenotype. This polarization is crucial, as classical macrophages play a well-recognized role in differentiating type-1 immune responses and resisting Leishmania infection.

Objective: The present study aims to evaluate the anti-leishmanial immunoadjuvant effects of the miR-155 chitosan polyplex (miR-155 CP).

Methods: The anti-leishmanial immunoadjuvant activity of miR-155 CP synthesized by the coacervation method was assessed against L. major (MRHO/IR/75/ER) by analyzing the infectivity rate on RAW 264.7 cells in vitro.MiR-155 CP as an adjuvant co-administrated with soluble Leishmania antigen (SLA) for immunization of BALB/c mice, then the challenge was performed by subcutaneous injection of 1 × 10⁶ L. major promastigotes. Eight weeks following the challenge, lesion size, parasite load, cytokine assay, and nitric oxide production were evaluated.

Results: The nanoparticles were produced with a size of 233.87 ± 8 nm and a zeta potential of + 22.6 ± 2 mV with good transfection efficiency. The mean infection index among pretreated cells with miR-155 CP (72±1.1) decreased significantly compared to the control group (420 ± 2.8). The parasite burden and the size of the lesions were significantly reduced in the immunized infected mice. Vaccination by miR-155 CP/SLA triggered the production of IFN-γ and NO and changed the cytokine profile of antigen-specific cells.Conclusion:The effectiveness of the SLA vaccine can be enhanced by including miR-155 CP as an adjuvant. SLA and miR-155 CP co-administration improve the type-1 immune response. This enhanced immune response helps prevent severe leishmaniasis.

Background: Like innate cells, B cells also express Pattern Recognition Receptors (PRRs) to detect danger signal such as tissue damage or pathogen intrusion. Production of specific antibodies by plasma cells results from the activation and differentiation of B cells following three signals: (i) antigen recognition by B Cell Receptors, (ii) recognition of danger and (iii) T-cell help. However, it is unclear whether T-cell help is dispensable for B cell activation and differentiation or not. Few studies have investigated the role of cytosolic PRRs such as NOD1 in B cell differentiation.

Methods: We used splenic C57BL6J B cells to evaluate NOD1 expression and then assessed the effect of stimulation with C12-iE-DAP, a NOD1 ligand, with or without CD40L as a T-cell help signal on B-cell responses globally or according to their CD23 expression level.

Results: We showed that murine B cells express NOD1 and that the presence of C12-iE-DAP induces activation, proliferation and initiates differentiation in plasma cells even in the absence of a T-dependent signal. Surprisingly, CD23^high B cells are more sensitive than CD23^low B cells to stimulation.

Conclusion: Our results suggest that the NLR pathway could induce antibody development during infections and be exploited to develop more effective vaccination.

Background: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and current treatments are limited by high toxicity and low survival rates, highlighting the need for new therapeutic approaches. Natural killer (NK) cells can identify and eliminate cancer cells without prior antigen exposure. Radiotherapy directly targets tumors and increases activating ligands on tumor cells, promoting NK cell interactions. Cetuximab, an EGFR-targeting antibody, enhances NK cell cytotoxicity. Additionally, anti-PD-1 antibodies may further boost NK cell function by blocking inhibitory signals. The study aimed to enhance HNSCC treatment efficacy by combining radiotherapy and targeted therapy with expanded NK cells.

Methods: NK cells were isolated, activated, and expanded from healthy donors. The FaDu and SCC-47 cell lines were inoculated into NOD/SCID mice. The mice were treated with PD-1 inhibitors, cetuximab, and radiation, followed by intravenous injection of NK cells.

Results: Radiation increased ligands that regulate NK cell sensitivity. The combination of cetuximab, radiotherapy, and expanded NK cells significantly suppressed cancer progression and improved survival rates. However, adding anti-PD-1 antibodies did not further enhance outcomes.

Conclusion: This study suggests that a multimodal approach combining cetuximab, radiotherapy, and NK cells can significantly improve HNSCC therapy efficacy, offering a novel and promising treatment strategy.

Background: Buserelin has been used to treat central precocious puberty (CPP). However, it could potentially result in immune dysregulation to undermine patients' health. Therefore, it is necessary to elucidate the effects of buserelin on immune cells. Here we explored buserelin-induced impacts on the differentiation and function of macrophage-colony-stimulating factor-producing T helper (ThGM) cells to uncover the immunoregulatory role of buserelin.

Methods: Rat CPP was induced by danazol injection followed by buserelin treatment. The frequencies of ThGM cells in the spleen and lymph nodes were evaluated by flow cytometry. ThGM cell generation and function were analyzed in cell culture assays. Cell signaling was measured by Immunoblotting.

Results: Buserelin increased the frequencies of splenic and lymph node ThGM cells. Buserelin promoted the in vitro differentiation and proliferation of ThGM cells. Buserelin-treated ThGM cells showed stronger supportive effects on other effector T helper cells. Buserelin induced the activation of the nuclear factor of activated T cells and extracellular signal-regulated kinase 1/2 in ThGM cells.

Conclusion: Buserelin enhances the differentiation and function of pro-inflammatory ThGM cells, thus increasing the risk of autoimmune or inflammatory disorders. Therefore, it is necessary to monitor ThGM cells in buserelin-treated children to prevent latent immune dysregulation.

Background: Most of the investigations related to inflammasome activation during HIV infection have focused on the receptor NLRP3 and innate immune cells such as monocytes/macrophages. However, during the past years, inflammasome activation has also been explored in lymphocytes, and novel sensors, other than the NLRP3, have been shown to play a role in the biology of these cells. Here, we hypothesized that NLRP1 may be involved in CD4+ T cell dysregulation in people living with HIV (PLWH), therefore contributing to chronic inflammation and to the pathogenesis of non-HIV-associated diseases.

Methods: The activation of NLRP1 in CD4+ T cells was assessed ex-vivo and in-vitro by the meaning of anti-CD3/anti-CD28 and Talabostat/Val-boroPro (VbP) response.

Results: Our results showed that the NLRP1 inflammasome was activated in PLWH CD4+ T cells, and that the stimulation of CD4+ T cells resulted in increased response to anti-CD3/anti-CD28 and VbP. Functional variants in NLRP1 significantly affected the level of inflammatory dysregulation of CD4+ T cells, therefore explaining at least in part the association with CD4+ T-mediated diseases.

Conclusion: PLWH CD4+ T cells are more prone to IL-1β release and pyroptosis, therefore contributing to chronic inflammation.

Introduction: Preeclampsia is a serious pregnancy complication that can lead to life-threatening conditions such as seizures, strokes, and even death. A dysregulated inflammatory response in the placenta plays a crucial role in the development of preeclampsia. Cordycepin, known for its anti-inflammatory and antioxidant properties, was the focus of this study, which aimed to investigate its effects on preeclampsia.

Methods: A preeclampsia-like rat model was established via tail vein injection of lipopolysaccharides (LPS) at a dose of 1 μg/kg in pregnant rats. These rats were then treated with cordycepin at doses of 5, 25, or 50 mg/kg from embryonic day 6 (E6) today 18 (E18). Systolic blood pressures and urinary protein levels were monitored, and pregnancy outcomes, such as fetal body length and weight, were measured. The expression of target genes or proteins was assessed by qPCR, ELISA, and Western blot.

Results: Our findings revealed that cordycepin significantly reduced systolic blood pressure and proteinuria in preeclampsia-like rats. Additionally, cordycepin improved pregnancy outcomes, as shown by increased fetal body length and weight. The treatment also lowered serum sFlt-1 levels, elevated PIGF levels, decreased placental pro-inflammatory cytokine levels (IL-1β, TNF-α, IL-6, MCP-1, and MIP-2), and raised levels of anti-inflammatory cytokine IL-10 level in preeclampsia-like rats. Furthermore, cordycepin helped restore macrophage population imbalances, increasing M1-type macrophage markers (iNOS, TNF-α, and IL-1β) and reducing M2-type macrophage markers (Arg 1, IL-10, and TGF-β).

Conclusion: This study suggests that cordycepin alleviates LPS-induced preeclampsia by reducing placental inflammation and correcting the M1/M2 macrophage imbalance, offering potential therapeutic benefits for managing preeclampsia.

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of inflammatory bowel disease (IBD) with rapidly increased incidence worldwide. Although multiple factors contribute to the occurrence and progression of IBD, the role of intestinal fungal species (gut mycobiota) in regulating the severity of these conditions has been increasingly recognized. C-type lectin receptors (CLRs) on hematopoietic cells, including Dectin-1, Dectin-2, Dectin-3, Mincle and DC-SIGN, are a group of pattern recognition receptors (PRRs) that primarily recognize fungi and mediate defense responses, such as oxidative stress. Recent studies have demonstrated the indispensable role of CLRs in protecting the colon from intestinal inflammation and mucosal damage.

Methods and results: This review provides a comprehensive overview of the role of CLRs in the pathogenesis of IBD. Given the significant impact of mycobiota and oxidative stress in IBD, this review also discusses recent advancements in understanding how these factors exacerbate or ameliorate IBD. Furthermore, the latest developments in CLR-guided IBD therapy are examined to highlight the modulation of CLRs in fungal recognition and oxidative burst during the IBD process.

Conclusion: This review emphasizes the importance of CLRs in IBD, offering new perspectives on the etiology and therapeutic approaches for this disease.