To investigate the autoimmune mechanisms of schizophrenia, we explored the relationship between schizophrenia and cancer using gene expression data of peripheral blood mononuclear cells from GSE27383 datasets. Gene screening and enrichment analysis using Gene Set Enrichment Analysis were applied to identify possible connections between schizophrenia and cancer. Real-time PCR (quantitative PCR), Western blotting and immunohistochemistry were performed on the brain tissue from both schizophrenia patients and normal controls. The genes for IL-8, as well as PTGS2, TPR, JUN, CXCL1, CXCL3, CXCL5 and PARD3 were highly expressed in schizophrenia patients. Cancer and chemokine signaling pathways were enriched in the schizophrenic group, related to the high expression of IL-8. Increased expression of IL-8 was further confirmed by quantitative PCR, Western blotting and immunohistochemistry results. Our results suggest that IL-8 may participate specifically in the pathophysiological changes that occur in schizophrenia. Additionally, our findings provide novel evidence supporting the autoimmune hypothesis of schizophrenia.

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed.Colony-stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated.Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

Lumbar degenerative disc disease (DDD) is a multifaceted progressive condition and often accompanied by disc herniation (DH) and/or degenerative spondylolisthesis (DS). Given the high prevalence of the disease (up to 20% according to some estimates) and the high costs associated with its care, there is a need to explore novel therapies such as regenerative medicine. Exploring these novel therapies first warrants investigation of molecular pathways underlying these disorders. Here, we show results from next generation RNA sequencing (RNA-seq) on mRNA isolated from 10 human nucleus pulposus (NP) samples of lumbar degenerated discs (DH and DS; n=5 for each tissue) and other musculoskeletal tissues (Bone, cartilage, growth plate, and muscle; n=7 for each tissue). Pathway and network analyses based on gene ontology (GO) terms were used to identify the biological functions of differentially expressed mRNAs. A total of 701 genes were found to be significantly upregulated in lumbar NP tissue compared to other musculoskeletal tissues. These differentially expressed mRNAs were primarily involved in DNA damage, immunity and G1/S transition of mitotic cell cycle. Interestingly, DH-specific signaling genes showed major network in chemotactic (e.g., CXCL10, CXCL11, IL1RL2 and IL6) and matrix-degrading pathway (e.g., MMP16, ADAMTSL1, 5, 8, 12, and 15), while DS-specific signaling genes were found to be those involved in cell adhesion (e.g., CDH1, EPHA1and EFNA2) and inflammatory cytokines (e.g., CD19, CXCL5, CCL24, 25 and XCL2). Our findings provide new leads for therapeutic drug discovery that would permit optimization of medical or pharmacological intervention for cases of lumbar DDD.

A systems approach was used to explore the genome and transcriptome of Mycobacterium shigaense, a new opportunistic pathogen isolated from a patient with a skin infection, and the host response transcriptome was assessed using a macrophage infection model. The M. shigaense genome comprises 5,207,883 bp, with 67.2% G+C content and 5098 predicted coding genes. Evolutionarily, the bacterium belongs to a cluster in the phylogenetic tree along with three target opportunistic pathogenic strains, namely, M. avium, M. triplex and M. simiae. Potential virulence genes are indeed expressed by M. shigaense under culture conditions. Phenotypically, M. shigaense had similar infection and replication capacities in a macrophage model as the opportunistic species compared to M. tuberculosis. M. shigaense activated NF-κB, TNF, cytokines and chemokines in the host innate immune-related signaling pathways and elicited an early response shared with pathogenic bacilli except M. tuberculosis. M. shigaense upregulated specific host response genes such as TLR7, CCL4 and CXCL5. We performed an integrated and comparative analysis of M. shigaense. Multigroup comparison indicated certain differences with typical pathogenic bacilli in terms of gene features and the macrophage response.

Pashmina goat (Capra hircus) is an economically important livestock species, which habitats the cold arid desert of the Ladakh region (India), and produces a princely animal fiber called Pashmina. The Pashmina goat has a double coat fleece as an adaptation to the very harsh cold winters the outer long coarse hair (guard hair) produced from primary hair follicles and the inner fine Pashmina fiber produced from secondary hair follicles. Pashmina fiber undergoes a circannual and synchronized growth cycle. In the present study, we analyzed transcriptome profiles from 10 different Pashmina goats during anagen and telogen to delineate genes and signaling pathways regulating active (anagen) and regressive (telogen) phases of the follicle growth. During anagen, 150 genes were expressed at significantly higher levels with log (FC) > 2 and p_adj < 0.05. The RNA seq results were subjected to qRT-PCR validation. Among the nine genes selected, the expression of HAS1, TRIB2, P2RX1. PRG4, CNR2, and MMP25 were significantly higher (p < 0.05) in the anagen phase, whereas MC4R, GIPC2, and CDO1 were significantly expressed (p < 0.05) in the telogen phase which supports and validates the gene expression pattern from the RNA-sequencing. Differentially expressed genes revealed that Pashmina fiber initiation is largely controlled by signaling pathways like Wnt, NF-Kappa, JAK-STAT, Hippo, MAPK, Calcium, and PI3K-Akt. Expression of genes from the Integrin family, Cell adhesion molecules, and ECM-receptors were observed to be at much higher levels during anagen. We identified key genes (IL36RN, IGF2, ITGAV, ITGA5, ITCCR7, CXCL5, C3, CCL19, and CXCR3) and a collagen cluster which might be tightly correlated with anagen-induction. The regulatory network suggests the potential role of RUNX3, NR2F1/2, and GATA family transcription factors in anagen-initiation and maintaining fiber quality in Pashmina goats.

Cancer treatment with doxorubicin (DOX) can induce cumulative dose-dependent cardiotoxicity. Currently, there are no specific biomarkers that can identify patients at risk during the initial doses of chemotherapy. The aim of this study was to examine plasma cytokines/chemokines and potential cardiovascular biomarkers for the prediction of DOX-induced cardiotoxicity. Plasma samples were collected before (T0), and after the first (T1) and the second (T2) cycles of DOX-based chemotherapy of 27 breast cancer patients, including five patients who presented with >10% decline of left ventricular ejection fraction (LVEF), five patients with LVEF decline of 5-10%, and 17 patients who maintained normal LVEF at the end of chemotherapy (240 mg/m2 cumulative dose of DOX from four cycles of treatment). Multiplex immunoassays were used to screen plasma samples for 40 distinct chemokines, nine matrix metalloproteinases, 33 potential markers of cardiovascular diseases, and the fourth-generation cardiac troponin T assay. The results showed that the patients with abnormal decline of LVEF (>10%) had lower levels of CXCL6 and sICAM-1 and higher levels of CCL23 and CCL27 at T0; higher levels of CCL23 and lower levels of CXCL5, CCL26, CXCL6, GM-CSF, CXCL1, IFN-γ, IL-2, IL-8, CXCL11, CXCL9, CCL17, and CCL25 at T1; and higher levels of MIF and CCL23 at T2 than the patients who maintained normal LVEF. Patients with LVEF decline of 5-10% had lower plasma levels of CXCL1, CCL3, GDF-15, and haptoglobin at T0; lower levels of IL-16, FABP3, and myoglobin at T1; and lower levels of myoglobin and CCL23 at T2 as compared to the patients who maintained normal LVEF. This pilot study identified potential biomarkers that may help predict which patients are vulnerable to DOX-induced cardiotoxicity although further validation is needed in a larger cohort of patients. Impact statement Drug-induced cardiotoxicity is one of the major concerns in drug development and clinical practice. It is critical to detect potential cardiotoxicity early before onset of symptomatic cardiac dysfunction or heart failure. Currently there are no qualified clinical biomarkers for the prediction of cardiotoxicity caused by cancer treatment such as doxorubicin (DOX). By using multiplex immunoassays, we identified proteins with significantly changed plasma levels in a group of breast cancer patients who were treated with DOX-based chemotherapy and produced cardiotoxicity. These proteins were associated with immune response and were identified before DOX treatment or at early doses of treatment, thus they could be potential predictive biomarkers of cardiotoxicity although further validation is required to warrant their clinical values.

Adiponectin is an adipokine with a modulatory role in metabolism and exerting both anti- and pro-inflammatory effects. Levels of adiponectin are increased in serum and synovial fluid from patients with rheumatoid arthritis (RA). Adiponectin is able to stimulate the production of different pro-inflammatory factors from peripheral blood mononuclear cells (PBMCs) and fibroblast-like synoviocytes (FLS) from subjects with established RA. As increased circulating adiponectin levels are a risk factor for future development of RA in subjects with obesity, we hypothesize that adiponectin is implicated in the development of RA at an early stage by initiating the pro-inflammatory processes associated with the disease pathogenesis. Therefore, we aimed to determine if adiponectin is able to induce pro-inflammatory responses in cells involved in the pathogenesis of RA, but collected from subjects without any known inflammatory disease. PBMCs and FLS were obtained from non-inflamed subjects and stimulated with 5 μg/ml human recombinant adiponectin. Supernatants collected after 48 h were analyzed for the production of 13 chemokines and 12 cytokines using multiplex assay and ELISA. Adiponectin significantly stimulated the production of CXCL1, CXCL5, and interleukin (IL)-6 in both PBMCs and FLS, whereas it induced CCL20, CCL4, CCL3, CCL17, tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor and IL-10 only in PBMCs, and CXCL8, CXCL10, CCL5, CCL11, and CCL2 only in FLS. Pre-stimulation with TNF of FLS from non-inflamed subjects did not significantly enhance the release of most pro-inflammatory factors compared to adiponectin alone. Our findings indicate that PBMCs and FLS from non-inflamed subjects react to adiponectin stimulation with the secretion of several pro-inflammatory chemokines and cytokines. These results suggest that adiponectin is able to initiate pro-inflammatory responses in cells from non-inflamed subjects and support the hypothesis that adiponectin is implicated in the early phases of RA pathogenesis.

Keywords: adiponectin; chemokines; cytokines; fibroblast-like synoviocytes; inflammation; peripheral blood mononuclear cells.

Primary ciliary dyskinesia (PCD), cystic fibrosis (CF), and chronic obstructive airway disease are characterized by neutrophilic inflammation in the lungs. In CF and chronic obstructive airway disease, improper functioning of neutrophils has been demonstrated. We hypothesized that the pulmonary damage in PCD might be aggravated by abnormal functioning neutrophils either as a primary consequence of the PCD mutation or secondary to chronic inflammation. We analyzed chemotactic responses and chemoattractant receptor expression profiles of peripheral blood neutrophils from 36 patients with PCD, 21 healthy children and 19 healthy adults. We stimulated peripheral blood monocytes from patients and healthy controls and measured CXCL8 and IL-1β production with ELISA. PCD neutrophils displayed reduced migration toward CXCR2 ligands (CXCL5 and CXCL8) in the shape change, microchamber and microslide chemotaxis assays, whereas leukotriene B4 and complement component 5a chemotactic responses were not significantly different. The reduced response to CXCL8 was observed in all subgroups of patients with PCD (displaying either normal ultrastructure, dynein abnormalities or central pair deficiencies) and correlated with lung function. CXCR2 was downregulated in about 65% of the PCD patients, suggestive for additional mechanisms causing CXCR2 impairment. After treatment with the TLR ligands lipopolysaccharide and peptidoglycan, PCD monocytes produced more CXCL8 and IL-1β compared to controls. Moreover, PCD monocytes also responded stronger to IL-1β stimulation in terms of CXCL8 production. In conclusion, we revealed a potential link between CXCR2 and its ligand CXCL8 and the pathogenesis of PCD.

CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-1β and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-1β gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-1β signaling pathway.

Head and neck squamous cell carcinoma (HNSCC) metastasizes to the locoregional lymph nodes at high rates and is related to poor clinical outcomes. However, the mechanism by which cancer cells migrate to the lymph nodes is unclear. To address this, we established a conditioned medium culture system for HNSCC cells and lymphatic endothelial cells (LECs) and investigated their crosstalk. Stimulation with tumor-conditioned medium (TCM) activated LECs, resulting in a robust increase in cell proliferation to induce lymphatic hyperplasia. Further, stimulation of HNSCC cells with activated LEC Conditioned media (TCM-LEC CM) induced cell invasion. Among various chemokines, CXCL5 promoted the invasion of TCM-LEC CM-treated HNSCC cells. The level of CXCL5 protein was higher in cancer tissues than those in normal tissues from HNSCC patients. Furthermore, treatment with SB225002, a CXCR2 (CXCL5 receptor) inhibitor, resulted in decreased lymph node metastasis in vivo. In conclusion, inhibition of CXCL5-CXCR2 signaling between cancer cells and LECs suppresses cancer cell invasion and metastasis in vitro and in vivo. This novel therapeutic strategy might be a practical approach to the clinical management of HNSCC.

Keywords: CXCL5; HNSCC; invasion; lymph node; migration.

Objectives: The objective of this study was to discover unknown differentially expressed genes (DEGs) associated with bronchopulmonary dysplasia (BPD), analyze their functions and enriched signaling pathways, and identify hub genes correlating with BPD incidence and evolvement.

Results: Of 1289 DEGs identified, 568 were downregulated and 721 were upregulated. The DEGs were mainly associated with oxidative stress, angiogenesis, extracellular matrix, inflammation, cell cycle, and protein binding. Eight DEGs were identified as hub genes, including C-X-C motif chemokine ligand 5 (Cxcl5), connective tissue growth factor (Ctgf), interleukin 6 (IL6), matrix metallopeptidase 9 (Mmp9), mitogen-activated protein kinase 14 (Mapk14), platelet and endothelial cell adhesion molecule 1 (Pecam1), TIMP metallopeptidase inhibitor 1 (Timp1), and TIMP metallopeptidase inhibitor 2 (Timp2). IL6 mRNA and protein expression levels were significantly increased in the peripheral blood of neonates with BPD.

Conclusions: Hence, BPD involves complex biological changes. Our findings indicate that inflammation and angiogenesis may play major roles in BPD pathogenesis and that IL6 has the potential to serve as a biomarker for early BPD diagnosis.

Keywords: Bioinformatics analysis; Bronchopulmonary dysplasia; IL6; Neonatal; Transcriptome.

Dual oxidase 1 (DUOX1) is an NADPH oxidase that is highly expre-ssed in respiratory epithelial cells and produces H₂O₂ in the airway lumen. While a line of prior in vitro observations suggested that DUOX1 works in partnership with an airway peroxidase, lactoperoxidase (LPO), to produce antimicrobial hypothiocyanite (OSCN^-) in the airways, the in vivo role of DUOX1 in mammalian organisms has remained unproven to date. Here, we show that Duox1 promotes antiviral innate immunity in vivo. Upon influenza airway challenge, Duox1 ^-/- mice have enhanced mortality, morbidity, and impaired lung viral clearance. Duox1 increases the airway levels of several cytokines (IL-1β, IL-2, CCL1, CCL3, CCL11, CCL19, CCL20, CCL27, CXCL5, and CXCL11), contributes to innate immune cell recruitment, and affects epithelial apoptosis in the airways. In primary human tracheobronchial epithelial cells, OSCN^- is generated by LPO using DUOX1-derived H₂O₂ and inactivates several influenza strains in vitro. We also show that OSCN^- diminishes influenza replication and viral RNA synthesis in infected host cells that is inhibited by the H₂O₂ scavenger catalase. Binding of the influenza virus to host cells and viral entry are both reduced by OSCN^- in an H₂O₂-dependent manner in vitro. OSCN^- does not affect the neuraminidase activity or morphology of the influenza virus. Overall, this antiviral function of Duox1 identifies an in vivo role of this gene, defines the steps in the infection cycle targeted by OSCN^-, and proposes that boosting this mechanism in vivo can have therapeutic potential in treating viral infections.

Keywords: DUOX1; Dual oxidase 1; hypothiocyanite; influenza; lactoperoxidase.

Rheumatoid arthritis (RA) is an autoimmune disease that causes physical disability in people worldwide. Despite progress made in RA treatment in the past decade, new drugs with high efficacy but few long-term adverse effects are still needed. This study focused on evaluating the therapeutic potential of α-mangostin on established collagen-induced arthritis (CIA) in DBA/1J mice. Arthritic DBA/1J mice were orally administered with two doses of α-mangostin (10 and 40 mg/kg) daily, for 33 days. Alpha-mangostin significantly decreased the clinical score in the short term at both doses and decreased the histopathological score at the higher dose. This improvement was accompanied by a reduction on serum levels of anti-collagen IgG2a autoantibodies and of the production of LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6 and IL-33 in the joints of CIA mice. Alpha-mangostin also exhibited an anti-oxidant effect decreasing the NADPH oxidase activity and lipid peroxidation and preserving the levels of reduced glutathione in the arthritic joints. In vitro this xanthone demonstrated modulatory properties on LPS-activated dendritic cells, although in Th1 and Th17-polarized lymphocytes promotes a pro-apoptotic phenotype. Altogether this study illustrates the capacity of α-mangostin to ameliorate the early clinical and histological signs of established CIA by reducing the inflammatory and oxidative responses.

The rupture of intracranial aneurysm (IA) is the leading cause for devastating subarachnoid hemorrhage. This study aimed to investigate genes related to IA and potential diagnosis targets. Two data sets (GSE15629 and GSE54083) were downloaded from Gene Expression Omnibus database. GSE15629 contained eight RI (ruptured IA), six UI (unruptured IA) and five control IA samples. GSE54083 included 8 RI, 5 UI and 10 superficial temporal artery samples. In total, 452 differentially expressed genes (DEGs) between RI and control, and 570 DEGs between UI and control, were identified. Protein-protein interaction networks for two kinds of DEGs related to RI and UI were constructed, respectively. Module networks were searched for DEGs related to RI or UI based on WGCNA (weighted gene coexpression network analysis). In the significant modules, FOS, CCL2, COL4A2 and CXCL5 were screened as crucial nodes with high degrees. Among them, FOS and CCL2 were enriched in immune response and COL4A2 was involved in the ECM (extracellular matrix) pathway, whereas CXCL5 was related to cytokine-cytokine receptor pathway. Taken together, FOS, CCL2, COL4A2 and CXCL5 might participate in the pathogenesis of RI or UI, and could serve as potential diagnosis targets.

TFF1, a mucin-associated secreted peptide of gastric mucous cells, is known as a protective agent for stomach epithelium under different stimuli, but its role upon Helicobacter infection is still not clear. In this paper we characterized TFFs expression, with particular attention to TFF1, under Helicobacter infection in gastric cell lines. A mouse model was used to distinguish TFF1 mRNA expression between acute and chronic stages of Helicobacter infection. Our results show that TFF1 expression is induced in infected cells; in addition, the inflammatory response upon Helicobacter infection is inversely associated to pre-existing TFF1 protein levels. In infected mice, TFF1 is initially upregulated in gastric antrum in the acute phase of infection, along with IL-1β and IL-6. Then, expression of TFF1 is gradually silenced when the infection becomes chronic and IFN-γ, CXCL5, and CXCL15 reach higher levels. Our data suggest that TFF1 might help cells to counteract bacteria colonization and the development of a chronic inflammation.

Cardiotrophin-1 (CT-1) is associated with cardiovascular (CV) diseases. We investigated the effect of CT-1 deficiency in the development and progression of atherosclerosis in double knockout Apoe^-/-ct-1^-/- mice. Apoe^-/- C57Bl/6 or Apoe^-/-ct-1^-/- C57Bl/6 mice were fed a normal chow diet (NCD) or a high-cholesterol diet (HCD). After sacrifice, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), free fatty acids and systemic paracrine factors were measured. Intraplaque lipid and collagen content were quantified in the aortic sections. Immune cell populations in spleen, lymph nodes and aorta were analysis by flow cytometry. Apoe^-/-ct-1^-/- mice in accelerated atherosclerosis exhibited a reduction of total cholesterol, LDL-C, atherosclerotic plaques size in the aortic root and in the abdominal aorta and improved plaque stability in comparison to Apoe^-/- mice. CT-1 deficiency in Apoe^-/- mice on (HCD) promoted atheroprotective immune cell responses, as demonstrated by a rise in plasma anti-inflammatory immune cell populations (regulatory T cells, Tregs; regulatory B cells, Bregs and B1a cells) and atheroprotective IgM antibodies. CT-1 deficiency in advanced atherosclerosis mediated regulation of paracrine factors, such as interleukin (IL)-3, IL-6, IL-9, IL-15, IL-27, CXCL5, MCP-3, MIP-1α and MIP-1β. In a model of advanced atherosclerosis, CT-1 deficiency induced anti-inflammatory and atheroprotective effects which resulted in abrogation of atheroprogression.

Background: Skin Cutaneous Melanoma (SKCM) is a tumor of the epidermal melanocytes induced by gene activation or mutation. It is the result of the interaction between genetic, constitutional, and environmental factors. SKCM is highly aggressive and is the most threatening skin tumor. The incidence of the disease is increasing year by year, and it is the main cause of death in skin tumors around the world. CXC chemokines in the tumor microenvironment can regulate the transport of immune cells and the activity of tumor cells, thus playing an anti-tumor immunological role and affecting the prognosis of patients. However, the expression level of CXC chemokine in SKCM and its effect on prognosis are still unclear.

Method: Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, DAVID 6.8, and Metascape were applied in our research.

Result: The transcription of CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL13 in SKCM tissues were significantly higher than those in normal tissues. The pathological stage of SKCM patients is closely related to the expression of CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. The prognosis of SKCM patients with low transcription levels of CXCL4, CXCL9, CXCL10, CXCL11, and CXCL13 is better. The differential expression of CXC chemokines is mainly associated with inflammatory response, immune response, and cytokine mediated signaling pathways. Our data indicate that the key transcription factors of CXC chemokines are RELA, NF-κB1 and SP1. The targets of CXC chemokines are mainly LCK, LYN, SYK, MAPK2, MAPK12, and ART. The relationship between CXC chemokine expression and immune cell infiltration in SKCM was closed.

Conclusions: Our research provides a basis for screening SKCM biomarkers, predicting prognosis, and choosing immunotherapy.

Keywords: CXC chemokine; microenvironment; prognostic biomarkers; skin cutaneous melanoma; therapeutic targets.

Malassezia yeast play a role in the pathogenesis of chronic dermatitis, especially in apocrine areas, by polarizing the local immunologic background to a Th2/Th17 state through aryl hydrocarbon receptor (AhR)-dependent pathways. Extra-mammary Paget's disease (EMPD) is an adenocarcinoma of apocrine origin, and except for cases associated with Malassezia yeast and their metabolites, the lesions typically develop in areas not exposed to environmental material. The purpose of this study was to investigate (a) the immunomodulatory effects of Malassezia metabolites on normal human keratinocytes (NHKCs), focusing on interleukin (IL)-17 and related cytokines/chemokines (IL-23, IL-36γ, CCL20), (b) the expression of these factors in lesion-affected skin in EMPD and (c) the activation of tumor-associated macrophages (TAMs) by these factors. Malassezia metabolites augmented the expression of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), CCL20 and IL-36γ mRNA in NHKCs in vitro. In lesion-affected skin of patients with EMPD, epidermal keratinocytes expressed CYP1A1 and CCL20. In addition, Paget cells expressed CCL20 and IL-23. IL-17-producing cells were distributed adjacent to Paget cells. Compared to healthy donors, patients with EMPD exhibited significantly increased serum levels of soluble (s)CD163, CXCL5, CXCL10 and CCL20. In addition, serum levels of sCD163 decreased significantly following tumor resection. Our study demonstrates a possible mechanism for the development of EMPD involving AhR-mediated signalling by epidermal keratinocytes and RANKL-induced recruitment of Th17 cells and TAMs.

An important component of vaccine development is the identification of safe and effective adjuvants. We sought to identify transcriptomal signatures of innate immune stimulating molecules using next-generation RNA sequencing with the goal of being able to utilize such signatures in identifying novel immunostimulatory compounds with adjuvant activity. The CC family of chemokines, particularly CC chemokines 1, 2, 3, 4, 7, 8, 17, 18, 20, and 23, were broadly upregulated by most Toll-like receptor (TLR) and nucleotide-binding domain and leucine-rich repeat-containing receptors (NLR) stimuli. Extracellular receptors such as TLR2, TLR4 and TLR5 induced the transcription of CXC chemokines including CXCL5, CXCL6 and CXCL8, whereas intracellular receptors such as TLR7 and TLR8 upregulated CXC chemokines 11 and 12. Both TLR1/2 and TLR2/6 agonists induced strong chemokine production in human peripheral blood mononuclear cells. Human skeletal muscle cells and fibroblasts respond with chemokine production only to TLR2/6 agonists, but not TLR1/2 agonists, consistent with strong expression of TLR2 and TLR6, but not of TLR1, in fibroblasts. TLR2/6 stimulated fibroblasts demonstrated functional chemotactic responses to human T cell and natural killer cells subsets. The activation of non-hematopoietic, adventitial cells such as fibroblasts and myocytes may contribute.

OBJECTIVE

The present study aimed to identify the genes involved in the pathogenesis of systemic lupus erythematosus (SLE) in Arabs by investigating a panel of 84 genes related to the t helper (Th)17-related regulatory network and to further explore the expression levels of serum interleukin (IL)-17A and IL-17F in a studied cohort. A comparative analysis of gene expression profile in SLE and lupus nephritis (LN) patients against that of healthy controls (HC) was performed.

METHODS

A quantitative real-time polymerase chain reaction (PCR) (Th17 autoimmunity and inflammation) array analysis was performed in peripheral white blood cells of 66 SLE patients under specific medical treatment and 30 age/gender/ethnically matched healthy controls. Statistical analysis was carried out using the RT(2) Profiler TM PCR Data Analysis tool.

RESULTS

The analysis of Th17 pathway revealed 14 genes (IL-17A, IL-17C, IL-17D, IL-17F, IL-18, IL-12RB2, IL-23R, CCL2, CCL20, CXCL5, MMP3, RORC, STAT4 and TRAF6) that are differentially expressed in SLE and HC (fold change [FC] < 2, P < 0.0006). No significant difference in expression profiles was observed between SLE and LN. A significant difference in serum concentration of IL-17A (P = 0.002) and IL-17F (P = 0.002) was observed between SLE (13.91 ± 4.25) and LN (18.26 ± 4.24).

CONCLUSIONS

Our study is the first to investigate a panel of 84 genes related to Th17 regulatory pathway in Arab SLE subjects and the first to explore the effect of current immunosuppression regimens on Th17 regulatory pathway. It paves the way for understanding the etiology of SLE and autoimmune diseases in general.

The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.

UNASSIGNED

Dengue virus (DENV) is transmitted by mosquito and has been circulating in Guangdong, China, for over 30 years. Dengue infection causes mild to severe disease symptoms in human. Cytokine profiles were suggested to be crucial especially during the acute stage in the dengue infection.

UNASSIGNED

To determine the cytokine profiles at the acute stage in patients with primary or secondary dengue infection in Guangzhou city in the 2014 outbreak.

UNASSIGNED

We investigated 23 inflammatory cytokines in serum collected from dengue-infected patients and analyzed their correlations with their clinical indexes.

UNASSIGNED

The concentrations of CXCL9, IP-10, CXCL11, IL-8, IL-10, and CCL2 in serum were significantly higher in the groups of DENV-infected patients during the first two weeks than those of control group while CCL17 and CXCL5 showed lower expression level in the patients. Among these cytokines, CXCL9, CCL17, and CXCL5 showed statistical difference between the groups of primary and secondary infections. The platelet count and lactate dehydrogenase were correlated with the level of CCL17 and MIP-1α/CXCL5, respectively, in the group of secondary infection.

UNASSIGNED

We determined the cytokine profiles in serum of the patients during the 2014 dengue outbreak. The expression of specific cytokines was associated with the secondary infection.