Modulation Of Immune Function Research Articles

Ex vivo-expanded human CD19+TIM-1+ regulatory B cells suppress immune responses in vivo and are dependent upon the TIM-1/STAT3 axis

Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10+ Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19+ B cells drives >900-fold expansion of IL-10+ B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19+CD73-CD25+CD71+TIM-1+CD154+ Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1+ and pSTAT3+ B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.

Phylogenomic characterization of the 2022 outbreak of monkeypox virus—The importance of sustained genetic surveillance

Phylogenomic characterization of the 2022 outbreak of monkeypox virus—The importance of sustained genetic surveillance

Safety and efficacy of Yupingfeng granules in children with recurrent respiratory tract infection: A randomized clinical trial.

ABSTRACTImportanceRecurrent respiratory tract infection (RRTI) is common in children. Inappropriate RRTI treatment will lead to asthma and other diseases, thereby seriously affecting the growth and physical health of children. Immune function modulation can prevent and alleviate childhood RRTI. Yupingfeng (YPF), a patented traditional Chinese medicine (TCM), has immunomodulatory effects and is widely used in China to treat children with RRTI.ObjectiveTo evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI.MethodsThis multicenter, randomized, double‐blind, double‐simulation, noninferiority clinical trial was conducted from January 2015 to August 2017, with an 8‐week treatment period and 52‐week follow‐up after the drug withdrawal. Children aged 2–6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups (2:2:1 ratio) to receive YPF, pidotimod, or placebo. The primary outcome was the proportion of RRTI returning to normal standard level during the follow‐up. The secondary outcomes were reduction in the number of RRTI recurrences, effect on clinical symptoms (in accord with TCM practice), effect per symptom, and safety. The trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn) under the unique identifier ChiCTR‐IPR‐15006847.ResultsThree hundred and fifty‐one children were enrolled and randomly assigned to 3 groups; 124, 125, and 61 children in the YPF, pidotimod, and placebo groups, respectively, had completed the trial. During the follow‐up, the proportion of RRTI returning to normal standard level was 73.13%, 67.15%, and 38.81% with YPF, pidotimod, and placebo, respectively (P < 0.0001). The proportion of cases who returned to normal standard level in the YPF group was 34.32% higher than that in the placebo group. The safety profile did not significantly differ among the groups.InterpretationYPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children, and were superior to placebo, with a high safety profile.

Hsa_circ_0046523 Mediates an Immunosuppressive Tumor Microenvironment by Regulating MiR-148a-3p/PD-L1 Axis in Pancreatic Cancer.

BackgroundCircular RNAs (circRNAs) are a novel type of non-coding RNA, play an important role in the progression of tumors. However, the function and mechanism of circRNAs in regulating immune microenvironment of pancreatic cancer (PC) remain largely unclear.MethodsThe effects of hsa_circ_0046523 expression on proliferation, migration and invasion of PC cells were analyzed by CCK8 and Transwell assays. Flow cytometry was used to detect the proportion of CD4+ T cells, CD8+ T cells and Tregs in peripheral blood mononuclear cells (PBMCs) after co-culture, and the apoptosis, depletion and function of CD8+ T cells. The expression levels of immunoregulatory cytokines were detected by enzyme linked immunosorbent assay (ELISA). The dual-luciferase reporter was performed to determine the interaction between hsa_circ_0046523, miR-148a-3p, and PD-L1. Rescue experiments and PD-L1 blocking experiments were employed to investigate whether hsa_circ_0046523 exerts its biological function by miR-148a-3p/PD-L1 in PC. Furthermore, an immunocompetent murine PC model was established to confirm these findings.ResultsHsa_circ_0046523 expression was remarkably upregulated in PC tissues and cell lines. Moreover, high expression of hsa_circ_0046523 was correlated with advanced pathological stage and poorer prognosis. Hsa_circ_0046523 overexpression promoted the proliferation, migration and invasion of PC cells in vitro. Co-culture experiments confirmed that forced expression of hsa_circ_0046523 could decrease the proportion of CD4+ and CD8+ T cells, as well as increase the proportion of Tregs among peripheral blood mononuclear cells (PBMCs). Meanwhile, hsa_circ_0046523 overexpression promoted the apoptosis and exhaustion of CD8+ T cells, inhibited CD8+ T cell function, increased the secretion of immunosuppressive cytokines IL-10 and TGF-β, and decreased the secretion of immune effector cytokines IFN-γ and IL-2 among PBMCs. Mechanistically, hsa_circ_0046523 exerted its biological function by binding to miR-148a-3p to upregulate PD-L1 expression in PC. Moreover, these immune modulating functions of miR-148a-3p/PD-L1 axis were also confirmed in an immunocompetent murine PC model.ConclusionsOur study suggests that hsa_circ_0046523/miR-148a-3p/PD-L1 regulatory axis mediates PC immunosuppressive microenvironment and these molecules are expected to be new targets for remodeling tumor immune microenvironment of PC.

Nutritional modulation of immune function: Analysis of evidence, mechanisms, and clinical relevance

Nutritional modulation of immune function: Analysis of evidence, mechanisms, and clinical relevance

The bioinformatics and experimental analysis of the novel roles of virus infection-associated gene CDC20 for prognosis and immune infiltration in hepatocellular carcinoma.

Infection virus including HBV and HCV has been well recognized as a major cause inducing hepatocellular carcinoma (HCC). However, molecular investigations into the HTLV-1 (Human T-lymphotropic virus type-1) and HCC have been rare. In this study, we integrated several public datasets of HCC patients and filtered seven genes including CDC20 as the HTLV-1 infection-related genes which were differentially expressed in HCC. CDC20 was chosen for further investigation based on its promising prognostic power. The expression profiles, prognostic assessment, association with clinicopathologic characteristics, prediction of correlated signal pathways, and the immune-modulating function of CDC20 were assessed. We found that CDC20 expression was significantly increased in hepatocellular carcinoma tissues and cell lines, and was correlated with histologic grade, pathologic stage, tumor status, and patient age. CDC20 exhibited prognostic value on overall survival and disease specific survival and was an independent prognostic factor. It was primarily involved in several signal pathways, especially the omega-hydroxylase P450 and epoxygenase P450 signal pathways. Moreover, CDC20 expression showed significant positive associations with the levels of several immune cells such as T helper 2 cells and follicular helper T cells, immunostimulators including TNFRSF18 and MICB, immunoinhibitors including KDR and PDCD1LG2, chemokines including XCL1 and CCL26, and chemokine receptors including CCR10 and CXCR3. This study for the first time delineated the correlation of CDC20 with HTLV-1 infection-associated HCC. The disorder of expression and function of CDC20 makes it a probable biomarker for better etiological classification, prognostic prediction, and precision medicine.

Vitamin D Supplementation Modulates Platelet-Mediated Inflammation in Subjects With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.

BackgroundRecently, our group identified increased platelet-mediated inflammation in type 2 diabetes (T2DM) patients, and it is a well-established risk factor for diabetes complications, particularly for the development of cardiovascular diseases (CVD). Furthermore, vitamin D is reported to play an important role in the modulation of platelet hyperactivity and immune function, although the effect of vitamin D on platelet-mediated inflammation is not well studied. Hence, we aimed to investigate the effect of vitamin D supplementation on platelet-mediated inflammation in T2DM patients.MethodsAfter screening a total of 201 subjects, our randomized, double-blind, placebo-controlled trial included 59 vitamin-D-deficient T2DM subjects, and the participants were randomly assigned to placebo (n = 29) or vitamin D3 (n = 30) for 6 months. Serum vitamin D metabolite levels, immunome profiling, platelet activation, and platelet–immune cell aggregate formation were measured at baseline and at the end of the study. Similarly, the serum levels of inflammatory cytokines/chemokines were assessed by a multiplex assay.ResultsSix months of vitamin D supplementation increases the serum vitamin D3 and total 25(OH)D levels from the baseline (p < 0.05). Vitamin D supplementation does not improve glycemic control, and no significant difference was observed in immune cells. However, platelet activation and platelet immune cell aggregates were altered after the vitamin D intervention (p < 0.05). Moreover, vitamin D reduces the serum levels of IL-18, TNF-α, IFN-γ, CXCL-10, CXCL-12, CCL-2, CCL-5, CCL-11, and PF-4 levels compared to the baseline levels (p < 0.05). Our ex vivo experiment confirms that a sufficient circulating level of vitamin D reduces platelet activation and platelet intracellular reactive oxygen species.ConclusionOur study results provide evidence that vitamin D supportive therapy may help to reduce or prevent the disease progression and cardiovascular risk in T2DM patients by suppressing oxidative stress and platelet-mediated inflammation.Clinical Trial RegistrationClinical Trial Registry of India: CTRI/2019/01/016921.

Calf Thymus Polypeptide Restrains the Growth of Colorectal Tumor via Regulating the Intestinal Microbiota-Mediated Immune Function.

Calf thymus polypeptide (CTP), with a molecular mass of <10 kDa, is prepared from the thymus of less than 30-day-old newborn cattle. In the present study, the inhibitory function of CTP in colorectal cancer (CRC) was investigated in B6/JGpt-Apc em1Cin(MinC) /Gpt (Apc Min/+) mice. CTP hampered tumor development and enhanced the ratio of CD3e−NK1.1+ cells by 113.0% and CD3e+CD28+ cells by 84.7% in the peripheral blood of Apc Min/+ mice. CTP improved the richness, diversity, and evenness of the intestinal microbiota of Apc Min/+ mice, particularly by regulating the abundance of immune-related microorganisms. CTP effectively regulated the expression of immune-related cytokines, such as interleukin (IL)-2 (15.19% increment), IL-12 (17.47% increment), and transforming growth factor (TGF)-β (11.19% reduction). Additionally, it enhanced the levels of CD4 and CD8, as well as the ratio of helper T lymphocytes (Th)1/Th2 in the spleen and tumors of Apc Min/+ mice. In CTP-treated mice, reduced levels of programmed death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), activated nuclear factor of activated T cells 1 (NFAT1), and nuclear factor κB (NF-κB) p65 signaling were noted. Collectively, the anti-CRC effect of CTP is related to the modulation of intestinal microbiota-mediated immune function, which provides a reference for CTP as a therapeutic drug or a combination drug used in CRC treatment in a clinical setting.

MiR-18a Mediates Immune Evasion in ER-Positive Breast Cancer through Wnt Signaling.

ER-positive (ER+) breast cancer is considered immunologically ‘silent’ with fewer tumor-infiltrating immune cells. We have previously demonstrated the role of miR-18a in mediating invasion and poor prognosis in ER+ breast cancer by activation of the Wnt signaling pathway. Here, we explored the immune-modulatory functions of high levels of miR-18a in these tumors. A microarray-based gene expression analysis performed in miR-18a over-expressed ER+ breast cancer cell lines demonstrated dysregulation and suppression of immune-related pathways. Stratification of the ER+ tumor samples by miR-18a levels in the TCGA and METABRIC cohort and immune cell identification performed using CIBERSORT and Immune CellAI algorithms revealed a higher proportion of T-regulatory cells (p < 0.001) and a higher CD4/CD8 ratio (p < 0.01). miR-18a over-expressed MCF7 co-cultured with THP-1 showed decreased antigen presentation abilities and increased invasiveness and survival. They also promoted the differentiation of pro-tumorigenic M2 macrophages. Inhibition of the Wnt pathway in miR-18a over-expressed cells brought about the restoration of TAP-1, a protein critical for antigen presentation. Examination of tumor specimens from our case series showed that miR-18a high ER+ tumors had a dense lymphocyte infiltrate when compared to miR-18a low tumors but expressed a higher CD4/CD8 ratio and the M2 macrophage marker CD206, along with the invasive marker MMP9. We report for the first time an association between miR-18a-mediated Wnt signaling and stromal immune modulation in ER+ tumors. Our results highlight the possibility of formulating specific Wnt pathway inhibitors that may be used in combination with immune checkpoint blockers (ICB) for sensitizing ‘immune-cold’ ER+ tumors to immunotherapy.

Immuno-modulating theranostic gold nanocages for the treatment of rheumatoid arthritis in vivo

The chronic autoimmune of rheumatoid arthritis (RA) usually results in inflammation of synovial joint, leading to pain, and destruction of cartilage and bone. Activated macrophages (M1 macrophages) actively take part in the RA pathogenesis, intensifying the inflammation and destruction of bone and cartilage. In this study, a nanoplatform was developed by grafting PEGylated folate acid (FA) and conjugating IL-4 onto gold nanocages (AuNCs), into the nanopores of which anti-inflammatory drug methylprednisolone (MP) was loaded. The IL-4@AuNCs conjugates (consisting of PEGylated FA, IL-4 and MP) effectively targeted the folate receptors overexpressed on M1 macrophage surface, down-regulating the expression of M1 marker and up-regulating the M2 markers. The expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β was significantly suppressed by the MP-AuNCs and IL-4@AuNCs both in vitro and in vivo. The AuNCs conjugates could act as a contrast agent for photoacoustic (PA) phantom and CT imaging. The therapeutic efficacy of different AuNCs conjugates on RA in a model of rat adjuvant-induced arthritis (AIA) was verified by ELISA, histological, and Western blot analyses, revealing the therapeutic potential through immune-modulatory function on macrophages with IL-4@AuNCs being the best and followed by MP-AuNCs.

The effect of alloferon on chemosensitivity of pancreatic cancer through the regulation of SLC6A14 expression

Abstract Pancreatic cancer is one of the most malignant solid tumors with a high mortality rate. Although there have been many trials for effective therapies using chemotherapeutic drugs, such as gemcitabine, pancreatic cancer still shows significantly higher mortality than other types of cancer. Therefore, it is needed to examine the effective therapeutic ways to improve conventional therapy for pancreatic cancer. It has been previously reported that cancer cells possess a high rate of glutamine uptake needed for their rapid proliferation. In addition, it has recently been reported that amino acid transporter SLC6A14 is up-regulated in some cancers in close relation to glutamine metabolism. Alloferon is a peptide isolated from the insect immune system and shows anti-viral and anti-inflammatory effects based on its immune modulating function. In addition, its anti-tumor effect was recently discovered, but the related mechanisms are largely unknown. For this reason, I investigated the effect of alloferon on pancreatic cancer cell lines Panc-1 and AsPC-1. When Panc-1 and AsPC-1 were exposed to alloferon for 3 weeks, I found down-regulation of SLC6A14 expression and decreased glutamine uptake. Given that SLC6A14 is involved in tumor progression and survival by promoting glutamine uptake into cancer cells, alloferon could be an effective way with conventional chemotherapeutic drug, gemcitabine. Therefore, alloferon could be a useful adjuvant for an effective therapeutic way with conventional chemotherapeutic drug, gemcitabine. This study was funded by the NRF of Korea (No.:2017R1A2B2010948, 2017R1A6A3A11032576, 2020R1C1C1009334)

Effect of bovine lactoferrin on seroconversion following polio vaccine administration in children: protocol for a double-blinded randomised controlled trial

IntroductionThe oral polio vaccine (OPV) has substantial results in eliminating wild poliovirus and the vaccine of choice in polio eradication. However, the mucosal immunity induced by the OPV is still...

MicroRNAs modulate Chlamydia trachomatis infection- and vaccine-induced immunity in macrophages

Abstract Recent studies indicate that microRNAs (miRNAs), including immune cell type-specific miRNAs modulate inflammation and immune response to Chlamydia trachomatis (CT) genital infection. However, the role of these miRNAs in modulation of immune cell function following CT infection or vaccine stimulation has not been investigated. We hypothesized that pretreatment of CT-infected and vaccine-stimulated macrophages with miRNA mimics or inhibitors will modulate secretion of inflammatory cytokines and expression of IFN-γ pathway-related genes. Thus, THP-1-differentiated macrophages (TDM) transfected with miRNA mimics or inhibitors were infected with CT or stimulated with a Vibrio cholerae ghost (rVCG)-based vaccine (rVCG-MECA) and the level of inflammatory cytokines secreted in culture supernatants was assessed by cytokine ELISA. Also, TDM expression of IFN-γ pathway-related genes was assessed by RT-qPCR. The results show that CT infection of TDM resulted in the downregulation of miR-15a, miR-29a, miR-146a and miR-222 while stimulation with rVCG-MECA resulted in their upregulation, as we previously reported. The level of TNF-α, IL-8, IL-1β and IFN-γ secreted by miRNA mimic- or inhibitor-treated TDM following infection or vaccine stimulation was dependent on the miRNA type. Furthermore, CT infection of untreated macrophages increased mRNA expression of INFGR1, JAK2, STAT1 and SOCS1. However, pretreatment of CT-infected cells with miR-146a mimic or inhibitor showed significantly decreased expression of these genes. The study demonstrated that miRNAs differentially modulate macrophage secretion of inflammatory cytokines and expression of IFN-γ pathway-related genes following CT infection or vaccine stimulation. Supported by None.

IL-27 Enhances γδ T Cell-Mediated Innate Resistance to Primary Hookworm Infection in the Lungs.

IL-27 is a heterodimeric IL-12 family cytokine formed by noncovalent association of the promiscuous EBI3 subunit and selective p28 subunit. IL-27 is produced by mononuclear phagocytes and unfolds pleiotropic immune-modulatory functions through ligation to IL-27 receptor α (IL-27RA). Although IL-27 is known to contribute to immunity and to limit inflammation after various infections, its relevance for host defense against multicellular parasites is still poorly defined. Here, we investigated the role of IL-27 during infection with the soil-transmitted hookworm, Nippostrongylus brasiliensis, in its early host intrapulmonary life cycle. IL-27(p28) was detectable in bronchoalveolar lavage fluid of C57BL/6J wild-type mice on day 1 after s.c. inoculation. IL-27RA expression was most abundant on lung-invading γδ T cells. Il27ra-/- mice showed increased lung parasite burden together with aggravated pulmonary hemorrhage and higher alveolar total protein leakage as a surrogate for epithelial-vascular barrier disruption. Conversely, injections of recombinant mouse (rm)IL-27 into wild-type mice reduced lung injury and parasite burden. In multiplex screens, higher airway accumulations of IL-6, TNF-α, and MCP-3 (CCL7) were observed in Il27ra-/- mice, whereas rmIL-27 treatment showed a reciprocal effect. Importantly, γδ T cell numbers in airways were enhanced by endogenous or administered IL-27. Further analysis revealed a direct antihelminthic function of IL-27 on γδ T cells as adoptive intratracheal transfer of rmIL-27-treated γδ T cells during primary N. brasiliensis lung infection conferred protection in mice. In summary, this report demonstrates protective functions of IL-27 to control the early lung larval stage of hookworm infection.

Dexamethasone, Interleukin 6, and the Adrenal Gland are the Real Battles for COVID-19: Our Molecular Docking, Physiological, and Immunological Explanations of Why the Clinical Benefit of Dexamethasone is More Evident in Males

More than two years have passed since the pandemic and despite all the efforts of researchers, the pathogenesis of the SARS-CoV-2 has not yet been resolved. The SARS-CoV-2 coronavirus that causes COVID-19 has high ability of mutation resulting in different variants of the virus. This mutation helps the virus bypass the body's immune defenses such as innate and adaptive immunity. Interleukin (Il-6), neutrophils, high ferritin, and high D dimer are crucial markers for all sorts of cells on the lengthy path to treatment of COVID-19. IL-6 is one of the key mediators of inflammation and viral cytokine storm in COVID-19 patients. In humans, interleukin (IL)-6 is a strong stimulator of the hypothalamic-pituitary-adrenal (HPA) axis at all levels, and it appears to have a pathogenic role in chronic stress and physiological aging. The adrenal glands have earned further recognition as key modulators of immune function, because secretory products of the adrenal glands. Dexamethasone inhibits TNF-α–induced IL-6 mRNA expression and protein secretion by reducing IL-6 mRNA stability. Although Dexamethasone provides benefits in patients with coronavirus disease but there is sex linked difference between male and female at response to this drug. It was showed that this drug might indeed have an effect in treating covid-19 but the clinical benefit of dexamethasone is more evident in males. Here we propose a testable hypothesis that dexamethasone may be effective in men better than female owing to two factors the first is the ability of males to induce high secretion of adrenal hormone under stress vs female. In males both stressors induced a significant increase, whereas in female adrenal e excretion remained on the same level under the two stress conditions. Both Adrenal e hormones and dexamethasone are hypothesized to promote blood neutrophil levels by increasing neutrophil exit from bone marrow, delaying neutrophil outflow from circulation, and lengthening the half-life of circulating neutrophils. Neutrophils a type of white blood cells that can downregulate interferon-stimulated genes, i.e., suppress their activity. When male patients received the steroid treatment, the dysregulated interferon signals went away quickly. But in female patients, the proportions of neutrophils were not as high and they did not react to the steroids in the same way. The second factor is that ACTH response to il-6 is stronger in males than females and ACTH was found to induce il-6. Therefore, male interact with dexamethasone better than females. Additionally, dexamethasone does not affect Il-6 secreted from the adrenal cortex, which allows Il-6 to be produced during stress and increase neutrophil ratio leading to stronger response in males. We need a new classification of IL-6 at physiological and pathological aspects, as the stimulatory factors are different. it was found that ACTH is h Endocrine Il-6 is stimulated by ACTH, but immune Il-6 is stimulated by il-1β and angiotensin II. Of note, dexamethasone critically saves COVID-19 patients but has no effect on Il-6 of endocrine (ACTH stimulated) origin, either basal or stimulated. We studied the molecular docking of dexamethasone with interleukin-6 and showed that the binding interaction of dexamethasone with interleukin-6 was with high binding affinity (-6.7 Kcal/mol)

Gut microbiome and prostate cancer

The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country. Lifestyle, especially diet, plays an important role in the development and progression of prostate cancer. Recent studies have revealed a connection between the gut microbiome and prostate cancer. A high-fat diet causes gut dysbiosis and gut bacterial metabolites, such as short-chain fatty acids and phospholipids that enter systemic circulation result in promoting prostate cancer growth. Additionally, the gut microbiota can serve as a source of testosterone, which affects prostate cancer progression. Men with castration-resistant prostate cancer have an increased abundance of gut bacteria with androgenic functions. Men with high-risk prostate cancer share a specific gut microbial profile and profiling gut microbiota could be a potentially effective tool to screen men with high-risk prostate cancer. Lifestyle modifications can improve the gut microbiome. Furthermore, altering the gut microbiome using prebiotic or probiotic interventions may prevent or delay prostate cancer development. Further study into the "Gut-Prostate Axis" would help in the discovery of new strategies for the prevention, screening, and treatment of prostate cancer.

Recombinant Active Peptides and their Therapeutic Functions.

Recombinant active peptides are utilized as diagnostic and biotherapeutics in various maladies and as bacterial growth inhibitors in the food industry. This consequently stimulated the need for recombinant peptides' production, which resulted in about 19 approved biotech peptides of 1- 100 amino acids commercially available. While most peptides have been produced by chemical synthesis, the production of lengthy and complicated peptides comprising natural amino acids has been problematic with low quantity. Recombinant peptide production has become very vital, costeffective, simple, environmentally friendly with satisfactory yields. Several reviews have focused on discussing expression systems, advantages, disadvantages, and alternatives strategies. Additionally, the information on the antimicrobial activities and other functions of multiple recombinant peptides is challenging to access and is scattered in literature apart from the food and drug administration (FDA) approved ones. From the reports that come to our knowledge, there is no existing review that offers substantial information on recombinant active peptides developed by researchers and their functions. This review provides an overview of some successfully produced recombinant active peptides of ≤100 amino acids by focusing on their antibacterial, antifungal, antiviral, anticancer, antioxidant, antimalarial, and immune-modulatory functions. It also elucidates their modes of expression that could be adopted and applied in future investigations. We expect that the knowledge available in this review would help researchers involved in recombinant active peptide development for therapeutic uses and other applications.

164P Immune modulatory functions of lurbinectedin in small cell lung cancer and malignant pleural mesothelioma patients

Lurbinectedin (Lur) is currently investigated in pre-treated patients (pts) with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). According to pre-clinical models, lur has the ability to induce anticancer immune responses. The immune-modulatory functions of lur in thoracic cancer pts have not been investigated yet.

Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment.

Mesenchymal stem cells (MSCs) have been increasingly used for treating autoimmune diseases due to their immune modulation functions, but inefficient homing to the target tissue and safety issues limits their wide application. Recently, increasing studies demonstrate small extracellular vesicles (sEVs) as key mediators of MSCs to exert their immunomodulatory effects. In this study, we found that sEVs derived from human umbilical cord MSCs stimulated by IFN-γ (IFNγ-sEVs) inhibited proliferation and activation of peripheral blood mononuclear cells and T cells in vitro. Furthermore, we confirmed that IFNγ-sEVs reduced psoriasis symptoms including thickness, erythema, and scales of skin lesions; exhausted Th17 cells, increased Th2 cells; and reduced enrichment of inflammatory cytokines such as IL-17A, IFN-γ, IL-6, and TNF-α in both spleen and skin lesions in vivo. Importantly, IFNγ-sEVs significantly improved the delivery efficiency and stability of ASO-210, the antisense oligonucleotides of miR-210 block the immune imbalance and subsequent psoriasis development. Our results reveal MSC-sEVs as promising cell-free therapeutic agents and ideal delivery vehicles of antisense oligonucleotides for psoriasis treatment.

Inflammation and immune dysfunction in Parkinson disease.

Parkinson disease (PD) is a progressive neurodegenerative disease that affects peripheral organs as well as the central nervous system and involves a fundamental role of neuroinflammation in its pathophysiology. Neurohistological and neuroimaging studies support the presence of ongoing and end-stage neuroinflammatory processes in PD. Moreover, numerous studies of peripheral blood and cerebrospinal fluid from patients with PD suggest alterations in markers of inflammation and immune cell populations that could initiate or exacerbate neuroinflammation and perpetuate the neurodegenerative process. A number of disease genes and risk factors have been identified as modulators of immune function in PD and evidence is mounting for a role of viral or bacterial exposure, pesticides and alterations in gut microbiota in disease pathogenesis. This has led to the hypothesis that complex gene-by-environment interactions combine with an ageing immune system to create the ‘perfect storm’ that enables the development and progression of PD. We discuss the evidence for this hypothesis and opportunities to harness the emerging immunological knowledge from patients with PD to create better preclinical models with the long-term goal of enabling earlier identification of at-risk individuals to prevent, delay and more effectively treat the disease.