The diagnostic accuracy of Th1 (IFN-?, TNF-?, and IL-2) and Th2 (IL-4, IL-6 and IL-10) cytokines response in AFB microscopy smear negative PTB- HIV co-infected patients.
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ABSTRACT:
SUBMITTER: Kisuya J
PROVIDER: S-EPMC6393479 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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Project description:IL-10 is an immunomodulatory cytokine with a critical role in limiting inflammation in immune-mediated pathologies. The mechanisms leading to IL-10 expression by CD4+ T cells are being elucidated, with several cytokines implicated. We explored the effect of IL-4 on the natural phenomenon of IL-10 production by a chronically stimulated antigen-specific population of differentiated Th1 cells. In vitro, IL-4 blockade inhibited while addition of exogenous IL-4 to Th1 cultures enhanced IL-10 production. In the in vivo setting of peptide immunotherapy leading to a chronically stimulated Th1 phenotype, lack of IL-4Rα inhibited the induction of IL-10. Exploring the interplay of Th1 and Th2 cells through co-culture, Th2-derived IL-4 promoted IL-10 expression by Th1 cultures, reducing their pathogenicity in vivo. Co-culture led to upregulated c-Maf expression with no decrease in the proportion of T-bet+ cells in these cultures. Addition of IL-4 also reduced the encephalitogenic capacity of Th1 cultures. These data demonstrate that IL-4 contributes to IL-10 production and that Th2 cells modulate Th1 cultures towards a self-regulatory phenotype, contributing to the cross-regulation of Th1 and Th2 cells. These findings are important in the context of Th1 driven diseases since they reveal how the Th1 phenotype and function can be modulated by IL-4.
| S-EPMC5595963 | biostudies-literature
Project description:BackgroundObesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA.ResultsThe serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI.ConclusionsQuantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.
| S-EPMC8237483 | biostudies-literature
Project description:BackgroundAlveolar echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis larval tapeworm infections in humans that severely impairs the health of affected patients in the northern hemisphere.MethodsThe expression levels of 20 cytokines associated with AE infection were measured by enzyme-linked immunosorbent assay, and the correlations between these cytokines were analysed in the R programming language.ResultsSerum cytokine levels differed among individuals in both the AE patient and healthy control groups. The results of the correlations among the cytokines showed obvious differences between the two groups. In the AE patients group, Th1 and Th2 cytokines formed a more complicated network than that in the healthy control group.ConclusionsThe altered correlations between Th1 and Th2 cytokines may be closely associated with AE infection, which may provide a new explanation for the essential differences between AE patients and healthy individuals.
| S-EPMC7294603 | biostudies-literature
Project description:Parasitic helminths establish chronic infections in mammalian hosts. Helminth/Plasmodium co-infections occur frequently in endemic areas. However, it is unclear whether Plasmodium infections compromise anti-helminth immunity, contributing to the chronicity of infection. Immunity to Plasmodium or helminths requires divergent CD4+ T cell-driven responses, dominated by IFN? or IL-4, respectively. Recent literature has indicated that Th cells, including Th2 cells, have phenotypic plasticity with the ability to produce non-lineage associated cytokines. Whether such plasticity occurs during co-infection is unclear. In this study, we observed reduced anti-helminth Th2 cell responses and compromised anti-helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co-infection. Using newly established triple cytokine reporter mice (Il4gfpIfngyfpIl17aFP635), we demonstrated that Il4gfp+ Th2 cells purified from in vitro cultures or isolated ex vivo from helminth-infected mice up-regulated IFN? following adoptive transfer into Rag1-/- mice infected with P. chabaudi. Functionally, Th2 cells that up-regulated IFN? were transcriptionally re-wired and protected recipient mice from high parasitemia. Mechanistically, TCR stimulation and responsiveness to IL-12 and IFN?, but not type I IFN, was required for optimal IFN? production by Th2 cells. Finally, blockade of IL-12 and IFN? during co-infection partially preserved anti-helminth Th2 responses. In summary, this study demonstrates that Th2 cells retain substantial plasticity with the ability to produce IFN? during Plasmodium infection. Consequently, co-infection with Plasmodium spp. may contribute to the chronicity of helminth infection by reducing anti-helminth Th2 cells and converting them into IFN?-secreting cells.
| S-EPMC4493106 | biostudies-literature
Project description:The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin. Primary keratinocytes from three donors (subjects 1, 2, and 3) were obtained and were either untreated (control) or exposed to cytokines (IL-4, IL-13, IFN-alpha, IFN-gamma and TNF). For the IL17A samples, primary keratinocytes were obtained from six donors, with cells derived from three donors treated with IL-17A and cells derived from the other three donors left untreated (i.e., unpaired control samples).
2012-03-07 | E-GEOD-36287 | biostudies-arrayexpress
Project description:Interleukin 31 receptor ? (IL-31RA) is a novel Type I cytokine receptor that pairs with oncostatin M receptor to mediate IL-31 signaling. Binding of IL-31 to its receptor results in the phosphorylation and activation of STATs, MAPK, and JNK signaling pathways. IL-31 plays a pathogenic role in tissue inflammation, particularly in allergic diseases. Recent studies demonstrate IL-31RA expression and signaling in non-hematopoietic cells, but this receptor is poorly studied in immune cells. Macrophages are key immune-effector cells that play a critical role in Th2-cytokine-mediated allergic diseases. Here, we demonstrate that Th2 cytokines IL-4 and IL-13 are capable of up-regulating IL-31RA expression on both peritoneal and bone marrow-derived macrophages from mice. Our data also demonstrate that IL-4R?-driven IL-31RA expression is STAT6 dependent in macrophages. Notably, the inflammation-associated genes Fizz1 and serum amyloid A (SAA) are significantly up-regulated in M2 macrophages stimulated with IL-31, but not in IL-4 receptor-deficient macrophages. Furthermore, the absence of Type II IL-4 receptor signaling is sufficient to attenuate the expression of IL-31RA in vivo during allergic asthma induced by soluble egg antigen, which may suggest a role for IL-31 signaling in Th2 cytokine-driven inflammation and allergic responses. Our study reveals an important counter-regulatory role between Th2 cytokine and IL-31 signaling involved in allergic diseases.
| S-EPMC4505597 | biostudies-literature
Project description:Objective This study aimed to explore cytokine serum levels and the ratio of type 1 T helper (Th1)/Th2 cells in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A total 245 patients diagnosed with AECOPD and 193 patients who progressed to stable COPD after the initiation of treatment in hospital were selected, while a further 50 healthy individuals served as controls. All patients with COPD were diagnosed using Global Initiative for Chronic Obstructive Lung Disease criteria. Serum concentrations of interleukin (IL)-2, interferon (IFN)-?, IL-4, IL-10, IL-17, and immunoglobulin (Ig)E were measured using enzyme-linked immunosorbent assays. Results AECOPD patients had higher levels of IL-2, IFN-?, IL-4, IL-10, IL-17, and IgE than those with stable COPD or controls. Intriguingly, the ratios of Th1/Th2 and IL-17/IgE were lower in AECOPD patients compared with the other two groups. These data suggest that AECOPD patients produce more IgE and have more differentiated Th2 cells than other groups. Conclusion Our findings suggest that an imbalance of circulating CD4+ T cell subsets correlates with AECOPD, and that a shift of Th1/Th2 and IL-17/IgE ratios may be caused by increased Th2 cell production.
| S-EPMC6136028 | biostudies-literature
Project description:ObjectiveMacmoondongtang has been used as a traditional medicine to treat pulmonary disease in Korea. However, the mechanism underlying its therapeutic effect has yet to be reported. In the present study, the role of macmoondongtang as a respiratory medicine, especially as an anti-asthmatic agent, has been attributed to the down-regulation of interleukin (IL)-4 and tumor necrosis factor (TNF)-α.Materials & methodsBALB/c mice were divided into five groups: control, asthma-induced control, dexamethasone treatment, treatment with 150 mg/kg macmoondongtang, and treatment with 1500 mg/kg macmoondongtang. To evaluate the anti-asthmatic effect of macmoondongtang, we investigated its suppressive or inhibitory effects against typical asthmatic changes such as differential cell count in bronchioalveolar fluid (BALF), serum IgE levels, lung morphology, expression of Th1/Th2 cell transcription factors such as T-bet and GATA-3, and Th1-/Th2-/Th17-related cytokines such as interferon (IFN)-γ, IL-12p40, IL-4, -5, -13, TNF-α, and IL-6. The active ingredients in macmoondongtang were further analyzed.ResultsMacmoondongtang treatment down-regulated serum IgE level, a very important marker of hyper-responsiveness. It reversed typical morphological changes such as mucous hypersecretion, lung epithelial cell hyperplasia, and inflammatory cell infiltration near bronchioalveolar space and veins. Macmoondongtang significantly decreased neutrophil count in BALF, as well as reduced T-bet, IFN-γ, and TNF-α expression in the lung. It also showed a dose-dependent control of inflammatory cells in BALF, controlled the expression of IL-12, IL-4, and IL-5 genes in the lung, and the protein expression of IL12p40, GATA-3, IL-4, IL-5, and IL-13. The component analysis revealed glycyrrhizin and liquiritin as the active ingredients.ConclusionsMacmoondongtang treatment alleviates asthma symptoms and modulate the Th1-/Th2- related cytokines. Glycyrrhizin and liquiritin could be the major the active therapeutic components.
| S-EPMC6886797 | biostudies-literature
Project description:The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin.
2012-03-07 | GSE36287 | GEO
Project description:Chronic low-grade inflammation plays a central role in the pathogenesis of osteoarthritis (OA), and several pro- and anti-inflammatory cytokines have been implicated to mediate and regulate this process. Out of these cytokines, particularly IFNγ, IL-1β, IL-4 and IL-17 are associated with different phenotypes of T helper (TH) cells and macrophages, both examples of cells known for great phenotypic and functional heterogeneity. Chondrocytes also display various phenotypic changes during the course of arthritis. We set out to study the hypothesis of whether chondrocytes might adopt polarized phenotypes analogous to TH cells and macrophages. We studied the effects of IFNγ, IL-1β, IL-4 and IL-17 on gene expression in OA chondrocytes with RNA-Seq. Chondrocytes were harvested from the cartilage of OA patients undergoing knee replacement surgery and then cultured with or without the cytokines for 24 h. Total RNA was isolated and sequenced, and GO (Gene Ontology) functional analysis was performed. We also separately investigated genes linked to OA in recent genome wide expression analysis (GWEA) studies. The expression of more than 2800 genes was significantly altered in chondrocytes treated with IL-1β [in the C(IL-1β) phenotype] with a fold change (FC) > 2.5 in either direction. These included a large number of genes associated with inflammation, cartilage degradation and attenuation of metabolic signaling. The profile of genes differentially affected by IFNγ (the C(IFNγ) phenotype) was relatively distinct from that of the C(IL-1β) phenotype and included several genes associated with antigen processing and presentation. The IL-17-induced C(IL-17) phenotype was characterized by the induction of a more limited set of proinflammatory factors compared to C(IL-1β) cells. The C(IL-4) phenotype induced by IL-4 displayed a differential expression of a rather small set of genes compared with control, primarily those associated with TGFβ signaling and the regulation of inflammation. In conclusion, our results show that OA chondrocytes can adopt diverse phenotypes partly analogously to TH cells and macrophages. This phenotypic plasticity may play a role in the pathogenesis of arthritis and open new therapeutic avenues for the development of disease-modifying treatments for (osteo)arthritis.
| S-EPMC8431052 | biostudies-literature