BMC Immunology最新文献

Background: The human interleukin-17 (IL-17) family comprises IL-17A to IL-17 F; their receptors are IL-17RA to IL-17RE. Evidence revealed that these cytokines can have a tumor-supportive or anti-tumor impact on human malignancies. The purpose of this study was to assess the expression of CXCR2, IL-17RA, and IL-17RC genes at the mRNA level as well as tissue and serum levels of IL-17A, vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β) in patients with bladder cancer (BC) compared to control.

Results: This study showed that gene expression of IL-17RA, IL-17RC, and CXCR2 in the tumoral tissue of BC patients was significantly upregulated compared with normal tissue. The findings disclosed a significant difference in the serum and tissue concentrations of IL-17A, VEGF, and TGF-β between the patient and the control groups, as well as tumor and normal tissues.

Conclusion: This study reveals notable dysregulation of CXCR2, IL-17RA, and IL-17RC genes, alongside changes in IL-17A, VEGF, and TGF-β levels in patients with BC than in controls. These findings indicate their possible involvement in BC development and their potential as diagnostic and therapeutic targets.

Background: The causal relationship between immune cells and telomere length remains controversial.

Methods: Data on the immune cells were obtained from a previous study with 3,757 participants. Data on telomere length were obtained from the OpenGWAS database. Genome-Wide Association Study (GWAS) data were obtained and screened for eligible instrumental variables (IVs) using the TwoSampleMR package and the Phenoscanner database. To investigate the genetic causality between immune cells and telomere length, Mendelian randomization (MR) analysis and Bayesian weighted Mendelian randomization (BWMR) analysis were used.

Results: MR analysis showed that there is indeed a genetic causal relationship between immune cells and telomere length. A total of 16 immune cells were successfully validated. A positive correlation was found between telomere length and immune cells such as CD28 + CD45RA + CD8br %CD8br (OR = 1.002, 95%CI: 1.000-1.003). A negative correlation was found between telomere length and immune cells such as Transitional AC (OR = 0.991, 95%CI: 0.984-0.997) (P < 0.05). Reverse MR analysis similarly confirmed that telomere length can affect four types of immune cells, including CD25 on IgD + CD24- (OR = 1.291, 95%CI: 1.060-1.571), at the genetic level.

Conclusion: There is indeed a mutual genetic causality between immune cells and telomere length, which will provide theoretical basis and support for more subsequent clinical studies.

Background: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared.

Methods: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push).

Results: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02).

Conclusions: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

Background: Itch sensitization has been reported in patients with chronic allergic skin diseases and observed in a mouse model of allergic contact dermatitis (ACD). There is evidence suggesting that neuroimmune interactions may contribute to itch sensitization, as an increase in dendritic cells (DCs) within ganglia has been observed during allergic conditions. However, how DCs interact with sensory neurons in ganglia during allergic conditions is still not known. This study aims to investigate the role of DCs in dorsal root ganglion (DRG) under ACD conditions, specifically focusing on itch sensitization within the DRG. The tolylene-2,4-diisocyanate (TDI) mouse model for ACD and the co-culture model of DCs and DRG neurons was employed in this study.

Results: We successfully induced ACD by TDI, as evidenced by the development of edema, elevated total serum IgE levels, and an observed itch reaction in TDI-sensitized mice. Calcium imaging and RT-qPCR analysis revealed that TDI-sensitized mice exhibited signs of peripheral sensitization, including a higher percentage of neurons responding to pruritogens and increased activation and expression of itch receptors in excised DRG of TDI-sensitized mice. Immunofluorescence and flow cytometric analysis displayed an increase of MHCII⁺ cells, which serves as a marker for DCs, within DRG during ACD. The co-culture study revealed that when DRG neurons were cultured with DCs, there was an increase in the number of neurons responsive to pruritogens and activation of itch receptors such as TRPA1, TRPV1, H1R, and TRPV4. In addition, the immunofluorescence and RT-qPCR study confirmed an upregulation of TRPV4.

Conclusions: Our findings indicate that there is an increase of MHCII⁺ cells and itch peripheral sensitization in DRG under TDI-induced ACD condition. It has been found that MHCII⁺ cells in DRG might contribute to the itch peripheral sensitization by activating itch receptors, as shown through co-culture studies between DRG neurons and DCs. Further studies are required to identify the specific mediator(s) responsible for peripheral sensitization induced by activated DCs.

Objective: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation.

Methods: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms.

Results: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model.

Conclusion: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

Background and aims: We aimed to investigate the immune characteristics of intestinal CD8⁺ gamma delta T (CD8⁺ γδ T) cells in Crohn's disease (CD) and their correlation with disease activity.

Methods: The study cohorts included 21 CD patients and 21 healthy individuals. CD8⁺ γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis.

Results: The study revealed a reduction in intestinal CD8⁺ γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8⁺ γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8⁺ γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR⁺ CD8⁺ γδT cell ratio, CD8⁺ γδT ratio, and CD8⁺ γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B⁺ CD8⁺ γδT cell and Perforin⁺ CD8⁺ γδT cell were identified as indicators that distinguish mildly moderately active CD cases.

Conclusions: Intestinal CD8⁺ γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8⁺ γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8⁺ γδ T cells can be used as indicators to assist in diagnosing CD patients.

Background: Haemoglobin (Hb) variants such as sickle cell trait (SCT/HbAS) play a role in protecting against clinical malaria, but little is known about the development of immune responses against malaria parasite (Plasmodium falciparum surface protein 230 (Pfs230) and Plasmodium falciparum erythrocyte binding antigen 175 region-3 (PfEBA175-3R)) and vector (on the An. gambiae Salivary Gland Protein-6 peptide 1 (gSG6-P1)) antigens in individuals with variants Hb genotypes. This study assessed antibody (IgG) responses against malaria parasite, Pfs230 and PfEBA175-3R and vector, gSG6-P1 in febrile individuals with variant Hb genotypes.

Methods: The study was conducted on symptomatic malaria patients attending various healthcare facilities throughout Ghana. Microscopy and ELISA were used to determine the natural IgG antibody levels of gSG6-P1, PfEBA175-3R & Pfs230, and Capillarys 2 Flex Piercing was used for Hb variants determination.

Results: Of the 600 symptomatic malaria patients, 50.0% of the participants had malaria parasites by microscopy. The majority 79.0% (398/504) of the participants had Hb AA, followed by HbAS variant at 11.3% (57/504) and HbAC 6.7% (34/504). There were significantly (p < 0.0001) reduced levels of gSG6-P1 IgG in individuals with both HbAC and HbAS genotypes compared to the HbAA genotype. The levels of gSG6-P1 IgG were significantly (p < 0.0001) higher in HbAS compared to HbAC. Similarly, Pfs230 IgG and PfEBA-175-3R IgG distributions observed across the haemoglobin variants were significantly higher in HbAC relative to HbAS.

Conclusion: The study has shown that haemoglobin variants significantly influence the pattern of anti-gSG6-P1, Pfs230, and PfEBA-175 IgG levels in malaria-endemic population. The HbAS genotype is suggested to confer protection against malaria infection. Reduced exposure to infection ultimately reduces the induction of antibodies targeted against P. falciparum antigens.