Immunology最新文献

Calcitonin gene-related peptide (CGRP) biases Langerhans cell (LC) Ag presentation to CD4⁺ T cells towards Th17-type immunity through actions on endothelial cells (ECs). We now report further evidence that IL-6 signalling at responding T cells mediates this effect. This CGRP effect was absent with ECs from IL-6 KO mice. Exposure of LCs, but not T cells, to IL-6 enhanced IL-6 and IL-17A production and reduced IFN-γ in the T-cell response. Pretreatment of LCs with IL-6 receptor α-chain (IL-6Rα) antibodies prior to IL-6 exposure significantly inhibited these responses. However, T-cell pretreatment with an IL-6/IL-6Rα chimera mimicked the effect of IL-6 pretreatment of LCs on T-cell responses. When this experiment was performed in the presence of the ADAM17 and ADAM10 inhibitor TAPI-1 during LC pretreatment of LCs and during the Ag presentation culture, release of soluble IL-6Rα chains into the medium was very significantly reduced, but this did not affect levels of T-cell cytokine release. Interestingly, LC exposure to IL-6 significantly increased LC IL-6 expression. Furthermore, pretreatment of T cells with antibodies against the IL-6 receptor β-chain significantly inhibited the IL-6 effect. CGRP may stimulate ECs in lymphatics and/or lymph nodes to produce IL-6 which likely results in migrating LCs nonclassically presenting IL-6. Furthermore, we found that IL-6 induces IL-6 production by LCs, suggesting an autocrine amplification pathway for this effect.

Tumour cell immune infiltration is linked to spindle pole component 25 (SPC25). The purpose of this work was to examine the function and molecular mechanism of SPC25 in immune escape in lung adenocarcinoma (LUAD). SPC25 expression in LUAD was examined using The Cancer Genome Atlas (TCGA) database, and RT-qPCR was used to confirm the results. The study involved the use of CD8⁺ T lymphocytes for immunoinfiltration analysis of SPC25, Gene Set Enrichment Analysis (GSEA) analysis of signalling pathways enriched by SPC25, identification of putative regulatory molecules of SPC25, and confirmation through the use of dual-luciferase and ChIP tests. To evaluate LUAD cell capacity for immune escape, a co-culture technique was employed. Measurements of glutamine uptake, glutamate and α-ketoglutarate levels, NADPH/NADP and GSH/GSSG ratios, and SLC1A5 expression were used to assess the levels of glutamine metabolism. LUAD had increased SPC25 expression. In LUAD cells, immune escape was facilitated by SPC25 knockdown, whereas overexpression had the reverse effect. SPC25 enrichment in the glutamine metabolism pathway was shown by GSEA analysis. Through increased glutamine metabolism brought on by SPC25 overexpression, immune escape was improved in LUAD and could be mitigated by GPNA therapy. E2F8 was also shown to be the transcription factor associated with SPC25, and they showed a binding interaction. By inhibiting glutamine metabolism through SPC25, knocking down E2F8 prevented immune escape in LUAD cells. On the other hand, the suppression of immune escape in LUAD cells caused by E2F8 knockdown was overcome by overexpression of SPC25. In LUAD, E2F8 stimulates SPC25 expression to facilitate glutamine metabolism and encourage immune escape. Our research validates a novel immune escape pathway driven by SPC25 in LUAD cells, providing LUAD patients with potentially effective immunotherapeutic approaches.

The purpose of this study was to compare the efficacy and safety of subcutaneous, sublingual, oral specific immunotherapy in patients who suffer from allergic conditions to pollen from trees, grasses and weeds, house dust mites and Alternaria alternata spores. A literature search was performed separately for each type of allergen and each administration route of the drug. As a result, it was found that all administration routes were quite effective. However, each type of immunotherapy was most effective for certain allergens. Subcutaneous and sublingual immunotherapy have proven effective for aeroallergens such as pollen from grass, trees, weeds and house dust mites. Despite this, subcutaneous immunotherapy had a number of disadvantages in the form of the duration of treatment and a greater prevalence of side effects. Some authors suggest that for allergies to house dust mites, the most effective method of immunotherapy was the subcutaneous method of administration, compared with sublingual and nasal. Sublingual therapy was safe enough for all types of allergens under study, however, to achieve the same effect as the subcutaneous method of administration. In addition, oral immunotherapy has been shown to be effective for food allergies with obvious symptoms of gastrointestinal disorders. In addition, oral immunotherapy is the only approved treatment for allergies in the elderly, due to the low risk of side effects. The time-accelerated and dosage-enhanced immunotherapy was also effective and safe. These data prove the effectiveness and safety of each administration route of specific allergens for specific immunotherapy in patients suffering from allergic rhinitis, bronchial asthma and even atopic dermatitis.

Many virus species, including Ebola virus, Marburg virus, SARS-CoV-2, dengue virus (DENV) and Zika virus (ZIKV), exploit CD209 and CD209L as alternative or attachment receptors for viral cis- or trans-infection. Thus, CD209 and CD209L may be critical targets for the development of therapeutic monoclonal blocking antibody drugs to disrupt the infection process caused by multiple viruses. Here, we produced a human chimeric monoclonal blocking antibody that simultaneously blocks CD209 and CD209L, namely 7-H7-B1. We show that 7-H7-B1 effectively blocks multiple pseudotyped or live viral infections in vitro, including SARS-CoV, SARS-CoV-2, Ebola virus, Marburg virus, ZIKV and DENV infections. However, the 7-H7-B1 mAb does not provide favourable protection against Zaire Ebola virus or ZIKV infection in hCD209 knock-in mice in vivo. Thus, our findings indicate that although CD209 and CD209L are critical for multiple viral infections in vitro, they may play only a partial role in viral infections in vivo.

Circadian rhythm is a physiological process that oscillates in a 24 h cycle. It has a complex connection with the function of the human immune system and even with the development of tumours. Previous studies demonstrated the time-dependent effects of chemotherapy and radiotherapy; however, there are few studies on the timing effects of immunotherapy. Here, we explored the differences in the efficacy of immune checkpoint inhibitors (ICIs) administered at different circadian rhythm times in non-small cell lung cancer (NSCLC). C57BL/6N lung Lewis cancer mice models were constructed. Then, mice were intraperitoneally injected with saline or anti-PD-1 antibody at 7 AM or 7 PM, The expression of PD-L1 was detected by flow cytometry, and the expressions of clock gene BMAL1 and PER2 were detected by polymerase chain reaction (PCR) after treatment. A retrospective analysis was conducted on patients with NSCLC who received ICIs in our department from June 2020 to December 2022. Animal experiments showed that mice treated with ICIs in the morning showed slower tumour growth and smaller tumour volumes than those in the afternoon, accompanied by increased expression of BMAL1 and PER2 and suppression of PD-L1 expression. Retrospective analysis showed that patients who received ICIs in the afternoon (after 12:00) had significantly longer progression-free survival than those in the morning (before 12:00) (median was 16.5 months versus 9.8 months, respectively, p = 0.031, hazard ratio = 1.87). These findings suggest that immunotherapy may have time dependence, offering a novel therapeutic strategy.

Nutritional zinc (Zn) deficiency could impair immune function and affect bowel conditions. However, the mechanism by which Zn deficiency affects the immune function of gut-associated lymphoid tissue (GALT) remains unclear. We investigated how Zn deficiency affects the function of GALT and level of secretory IgA (sIgA), a key component of the intestinal immune barrier, its underlying mechanisms, and whether Zn deficiency induces bacterial translocation to the liver. As previous research has indicated that interleukin (IL)-4 administration or Zn supplementation has a beneficial effect on the spleen of Zn-deficient rats, we investigated whether these supplements reverse the GALT immune system. Five-week-old male rats were fed a standard diet, Zn-deficient diet supplemented with saline or IL-4 for 6 weeks, or Zn-deficient diet followed by a standard diet for 4 weeks. Zn deficiency suppressed sIgA secretion in the intestinal tract by affecting GALT function and induced inflammatory responses through bacterial translocation to the liver via the portal vein. Furthermore, IL-4 administration and Zn supplementation in rats with Zn deficiency elicited comparable beneficial effects on GALT function, suggesting that the administration of either IL-4 or Zn could prevent inflammatory response via bacterial translocation to the liver.

Enterovirus A71 (EV-A71) has caused hand, foot, and mouth disease with an increased prevalence of neurological complications and acute mortality, threatening young children around the globe. By provoking mucosal immunity, intranasal vaccination has been suggested to prevent EV-A71 infection. However, antigens delivered via the nasal route usually fail to induce a protective memory response. Zymosan has been identified to activate multiple pattern recognition receptors to orchestrate innate and adaptive immunity. Herein, we aimed to investigate the capacity of zymosan to strengthen the vaccine response induced by an intranasal EV-A71 vaccine. First, we confirmed its remarkable capacity to ignite innate signaling by upregulating cytokine production in primary DCs in vitro. Second, we verified its capacity to promote the vaccine immunogenicity in vivo after triple vaccination with EV-A71, especially with the notable induction of virus-specific IgA at multiple mucosae and the IL-17-producing splenic population after antigen reencounter. Lastly, we validated its capacity to improve vaccine efficacy in vivo after dual vaccination by furnishing neonatal protection against lethal infection. Our findings show that zymosan, at a preferable dosage, could augment the benefits of the intranasal vaccination to tackle EV-A71 infection. This research provides a feasible strategy for preventing EV-A71 infection with severe complications and contributes to the development of nasal spray vaccination.