Methods: Peripheral blood mononuclear cells from 37 patients (age: 38.5 ± 9.8 years) with BD, and 25 healthy controls (HC) (age: 39.1 ± 9.3 years), were cultured in Th17-inducing conditions (IL-6, Phytohemagglutinin (PHA), IL-1β, and IL-23) for 6 days. Cultured cells were stained with CD4, CD8, CD3, TCR gamma/delta, CD19, interferon-γ (IFN-γ), and IL-17 antibodies to determine the intracellular cytokine secretion by flow cytometry.
Results: IL-17 expression by CD8+ and γδ+ T cells was higher in BD compared to HC (p = 0.004, p = 0.003, respectively). No differences were observed between the groups in the IL-17 production by B cells. Under Th17-inducing conditions, production of IFN-γ by CD4+, CD8+, and γδ+ T cells was also higher in BD compared to HC (p < 0.05 in all).
Conclusion: Our results suggest that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. More prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD might be associated with the increased innate responses, early tissue neutrophil infiltrations and late adaptive immunity in BD. 相似文献
Objectives: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD.
Patients and methods: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects. BD patients were divided into two groups according to their frequencies of oral ulcerations. NK cell cytotoxicity was determined using CD107a expression and a CFSE-based cytotoxicity test. Expression of NK cell receptors and surface markers and the intracellular IL-5, IL-10, IL-17, and IFN-γ levels in CD16+ NK cells were assessed by flow cytometry.
Results: Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells.
Conclusion: Increases in NK1/NK2 ratio and CD16+IFN-γ+ NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. 相似文献
Methods: To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators.
Results: The levels of various pro-inflammatory immune mediators (including MIF, TSLP, CCL2/MCP-1, CXCL9, CXCL10, IFN-β, IL-6, IL-17, IL-21, IL-22, and IL-23) were elevated in serum at the first time point, and decreased under immunosuppressive treatment. In parallel, the frequency of activated (CD86+) CD1c+ myeloid dendritic cells in blood was proportional to the central foveal thickness measured by optical coherence tomography.
Conclusions: These observations challenge the current view on the distinct pathophysiology of retinal degenerative and retinal inflammatory conditions in this patient. 相似文献
Methods: Cells were collected from vitreous cassettes and peripheral blood of 8 tubercular uveitis and 5 control subjects, undergoing vitrectomy and analyzed by flow cytometry for cellular composition, activation status, proinflammatory cytokine expression, and uptake of TLR9 ligand, CpG ODN 2216.
Results: CD3 + T cells with equal proportion of CD4+ and CD8 + T cells formed major fraction of infiltrating cells. The vitreous humor showed higher expression of recent activation marker, CD69, and proinflammatory cytokines, IFN-γ and IL-17A, in CD4 + T cells as compared to peripheral blood. Lastly, intraocular CD4 + T cells showed reduced uptake of ODN 2216 than peripheral blood.
Conclusions: Our results indicate that local antigenic stimuli trigger T cell infiltration and activation of CD4 + T cells that are hyporesponsive to TLR9 stimulation. These infiltrating T cells might be responsible in further aggravating ocular inflammation. 相似文献
Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.
Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.
Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.
Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases. 相似文献
Areas covered: We aim to review the available data from literature regarding the role of IL-23, with a more specific focus on the recent progresses in the therapeutic modulation of this cytokine.
Expert commentary: Increased knowledge regarding the role of IL-23 has allowed for the development of effective therapeutic progresses by blocking the IL-23 mediated pathways. Primary or secondary loss of response to anti-TNF therapies in Crohn’s disease patients during the first year is widely described in literature: the development of new drugs, with alternative mechanisms of action, is thus a key point to consider for the optimal management of these subjects. Drugs blocking the IL-12/23 pathway showed a good efficacy and safety profile in immune-mediated diseases Further studies are necessary regarding the role of the single blockade of IL-23. 相似文献
Methods: We evaluated the perioperative changes of T lymphocyte subsets in invasive breast cancer (IBC) patients and breast fibroadenoma (BF) patients preoperatively (preop) and 6, 24, 72 hours postoperatively (POH6, POH24, and POH72). Proportions of CD3, CD4, CD8, T helper (Th) 1, Th2, Th17 cells, regulatory T cells (Treg), and CD4+/CD8+, Th1/Th2 ratio were detected by flow cytometry. Changes in T helper cell quantity were correlated to clinicopathological parameters. Furthermore, we explored the association between the perioperative variations of T cell subsets and disease-free survival (DFS) of IBC patients.
Results: In IBC patients, Th1 cells diminished while Tregs elevated in postoperative 72 hours in the peripheral blood. In contrast, no significant perioperative changes of T cell subsets were observed in BF patients. Postoperative lower Th1 cells at POH 72 of IBC patients were correlated with greater tumor burden, HER2 positive and Ki67 positive. The increased Tregs at POH 72 of IBC patients were correlated with larger tumor size and HER2 positive. Th1 cell decline and Treg increment were both associated with shorter DFS in IBC patients.
Conclusions: The variations of peripheral T helper cell subsets showed postoperative immunosuppression and were associated with poor prognosis in IBC patients. 相似文献
Objective: We aimed to investigate the antiallergic potential of the Class A dioscorins of various yam species using the ovalbumin (OVA)-induced murine allergy model.
Materials and methods: We purified the recombinant Class A dioscorins (rDioscorins) of various yam species from Escherichia coli and evaluated their antiallergic potential by enzyme-linked immunosorbent assay.
Results: The Class A rDioscorins of various yam species suppressed allergic reactions by significantly decreasing the serum IgE and histamine levels. The serum IFN-γ and IgG2a levels significantly increased in all rDioscorin-treated mice. The splenocytes of the rDioscorin-treated mice also exhibited upregulated IFN-γ secretion in response to ConA stimulation. By contrast, the serum IL-5 levels decreased to basal levels in mice treated with Class A rDioscorins and the amount of IL-5 produced by splenocytes decreased in response to ConA stimulation.
Discussion: The Class A rDioscorins suppress allergic reactions, possibly through modulating an imbalanced Th1/Th2 immune response to OVA by promoting Th1 cell responses. Furthermore, the Class A rDioscorins of various yam species exhibited similar immunomodulatory activities in OVA-sensitized mice, which were different from the activities demonstrated by native dioscorins, suggesting that distinct immunomodulatory effects of native dioscorins on mice were attributed to the various isoforms in the yam tubers.
Conclusion: The Class A dioscorins of various yam species exhibit antiallergic activity and are potential immunotherapeutic agents for treating IgE-mediated hypersensitivity. 相似文献
Methods: Humoral and cellular immune responses of Balb/c mice to tetanus toxoid and cyclophosphamide, respectively, were used to monitor immunomodulatory activities of the ethanol leaf extract and fractions of M. aboensis at 200, 300 and 400 mg/kg. Active (butanol) fraction of the extract was subjected to chromatographic purifications to isolate the active compound and the structure elucidated by a combination of 1D and 2D NMR and mass spectrometry. Stimulation of specific T-lymphocytes using intracellular cytokine staining technique was used to evaluate immune-enhancing activity of the isolated compound.
Results: The extract and fractions evoked increase in both humoral and cellular immunity. At 400 mg/kg of butanol fraction, the normalized mean secondary production of IgG1 and IgG2a antibodies were 9.0 and 7.7, respectively. Serum cytokine production by butanol fraction following secondary challenge with tetanus toxoid showed that IL-12, IL-17A and IFN-γ were expressed by 48.14, 41.37 and 38.22%, respectively. Structural elucidation of the active compound revealed presence of isomeric mixtures of quercetin-3-O-rutinoside and quercetin-3-O-robinobioside (Compound 1a/b). Compound 1a/b exhibited in vitro upregulation of specific CD4+ T-lymphocytes that were largely IFNγ releasing with up to 43.7% stimulation at 6.25 μg/mL compared to the baseline effect in DMSO vehicle control group.
Conclusion: M. aboensis expressed strong immune-enhancing properties, which may explain its ethnopharmacological use in disease management. 相似文献
Areas covered: This review discusses the most updated studies on the complex pathogenic mechanisms of hidradenitis suppurativa and the relevant literature on the current treatment options for this condition.
Expert commentary: There is increasing evidence supporting the role of Th17 cells and enhanced expression of IL-17 and IL-1β, which represent potential targets for therapy. Bacteria and biofilms are likely contributory but secondary drivers of inflammation. There is also evolving evidence to suggest the presence of systemic comorbidities associated with HS, which underlie the importance of better understanding the pathogenesis and treatment of this disease. 相似文献
Objective: To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2).
Methods: The proliferation and cytotoxicity of NK cells cultured with Shikonin were detected with CCK-8 assay. The expressions of perforin, GranB and IFN-γ were examined with FCM. The content of TNF-alpha was disclosed with ELISA kit. p-ERK1/2 and p-Akt expression of NK cells were detected with western blot.
Results: With CCK-8 assay, it is found that Shikonin could significantly enhance NK cells proliferation and cytotoxicity to colon cancer cells. With FCM assay, it is found that Shikonin could improve the expression of perforin and GranB in a dose-dependent manner. Shikonin had no effect on TNF-alpha and IFN-γ expression. In mechanism, the study shows that Shikonin could enhance the expression of p-ERK1/2 and p-Akt.
Conclusions: Shikonin enhances NK cells proliferation and cytotoxicity via the improvement of perforin, GranB, p-ERK1/2 and p-Akt expression. 相似文献
Areas covered: Relevant references regarding the role of the IL-23/IL-17 pathway in the pathogenesis of psoriasis/psoriatic arthritis and clinical trials with IL-23p40 and IL-23p19 blocking agents were obtained through a literature search in MEDLINE/Pubmed for articles published until November 2016. Moreover, ongoing registered clinical trials (RCTs) of moderate-to-severe psoriasis and psoriatic arthritis were searched through clinicaltrials.gov website, and a manual search was made for pertinent communications at the 2016 American Academy of Dermatology and European Academy of Dermatology and Venereology meetings.
Expert commentary: There are potential advantages in selective blockade of the IL23-specific p19 subunit with respect to distal blockade of IL-17A or its receptor. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes -including IL-17F, IL-21 and IL-22-, in addition to IL-17A. On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease.
Specific IL-23p19 blockade with high-affinity monoclonal antibodies seems to be able to induce long-term remissions of the activity in psoriasis and might eventually represent a paradigm change in the treatment of psoriasis. The results of phase III and comparative head-to-head trials with these agents are eagerly awaited. 相似文献
Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP).
Patients and methods: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III). The phenotype and numbers of MDSCs were analyzed in peripheral blood of all the individuals and ascitic fluid of the patients using flow cytometry. Intracellular IFN-γ and serum alfa-fetoprotein were measured.
Results: Significant increases in the relative and the mean number of peripheral blood MDSCs were found in the cirrhosis and HCC groups than in the control group, with the HCC group showing the highest number. MDSC count was negatively correlated with IFN-γ levels, while α-FP was positively correlated with MDSC% in the HCC group. MDSC count was low in ascitic fluid of both HCC and cirrhosis groups with no significant difference between the 2 groups.
Conclusion: A high frequency of MDSCs was detected in the peripheral blood of cirrhotic and HCC patients, indicating presence of immunosuppressive arms. These cells could be targeted to develop a new effective immunotherapy or an adjuvant to current therapies. 相似文献
Areas covered: A PubMed search was performed for relevant literature. Among the trials of brodalumab, the most common adverse events included nasopharyngitis, headache, upper respiratory tract infection, and arthralgia. Suicidal ideation and completed suicides had been observed in the brodalumab programme, although evidence to date was quoted as not suggesting a causal association.
Expert commentary: By blocking the IL-17 receptor A, brodalumab antagonizes signaling from IL-17A, IL-17F, IL-17A/F and IL-25, and this probably contributes to the high efficacy observed in clinical trials. Considering the different therapeutic target and the potential biological implications that blocking IL-17RA instead of IL-17A might have, brodalumab may not necessarily belong to the same class that includes secukinumab and ixekizumab, but it may be classified in a distinct group. 相似文献
Objective: This study examines DHMEQ’s effect on therapeutic potential for atopic dermatitis (AD)-like lesions.
Materials and methods: AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice. The mice were then externally treated with DHMEQ ointment. Macroscopic and microscopic changes of the skin lesions were observed and recorded.
Results: DHMEQ inhibited ear swelling and relieved clinical symptoms of the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination illustrated that it significantly decreased DNCB/OX-induced epidermal thickness, the infiltration of inflammatory cells, and the count of mast cell. The elevated level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also suppressed by DHMEQ.
Discussion and conclusion: This study indicated that DHMEQ would be useful for the treatment of AD. 相似文献
Methods: A total of 29 explanted chronically rejected and 12 acutely rejected renal allografts were analyzed by immunohistochemistry. The distribution of TLOs, T cells, follicular dendritic cells, B cells, and follicular regulatory T (Tfr) cells, as well as Ki67, peripheral lymph node addressin (PNAd), podoplanin, AID, IL-17, IL-21, IL-10, and C4d expression were detected by immunohistochemistry. Correlations between lymphoid neogenesis and the expression of IL-17, IL-21, C4d, podoplanin, IL-10, and Foxp3 were evaluated. In addition, the duration of graft function was compared between allografts that harbored or lacked TLOs.
Results: TLOs were detected in 27.6% of chronically rejected renal grafts, but they rarely had germinal centers. Lymphoid neogenesis negatively correlated with CXCR5 expression, and almost completely correlated with IL-17 expression. Those grafts that harbored a TLO functioned for an average of 5.98 years and those without a TLO lasted only about half as long with an average of 2.91 years. However, in grafts that harbored a TLO, Foxp3+ cells were comparitively less than those without a TLO. Foxp3+CXCR5+ Tfr cells and IL-10+ cells were rare in grafts, irrespective of the presence of a TLO.
Conclusion: TLOs in chronically rejected kidney allografts may be an epiphenomenon of the inflammatory process that is related to graft duration. 相似文献
Methods: In this study, an EAE model with a clinical course containing acute onset, peak and chronic remission stages was established in C57BL/6J mice by myelin oligodendrocyte protein (MOG)35–55 peptide immunization, and followed by the monitoring of clinical and pathological parameters and autoreactive T cells at different stages during the course.
Results: The dynamic changes of inflammatory infiltration, myelin loss, and astrocyte proliferation in brain and spinal cord were highly consistent with clinical severity observed in EAE course. However, the frequencies of both MOG-specific CD4+ and CD8+ T cells in secondary lymphoid organs presented different dynamic trends from the IFN-γ production by MOG-reactive T cells. Meanwhile, the IL-17 production by MOG-reactive CD4+ T cells was consistent with the proliferation of MOG-specific CD4+ T cells.
Conclusions: Both CD4+ and CD8+ T cells were most sensitive to MOG antigen stimulation for IFN-γ production during the early stage of EAE, but then rapidly lost the function despite their vigorous proliferation at the peak stage and later. 相似文献
Objectives: We generated a monoclonal antibody (clone 1D1) against human CD86 (1D1) that could recognize both human and mouse CD86, and blocked the CD86/CD28 costimulatory pathway with our mAb on a murine lupus nephritis model induced with chronic graft-versus-host disease (cGVHD).
Materials and methods: Experimental lupus nephritis mice were induced with cGVHD, and splenocyte population were analyzed by flow cytometry. Autoantibodies and proteinuria were detected to evaluate the severity of lupus nephritis. The change of histopathology was observed by microscopy, fluorescence microscopy and electron microscopy.
Results: we successfully generated a monoclonal antibody against human CD86(1D1). 1D1 mAb could recognize not only human CD86, but also mouse CD86. 1D1 was applied to the cGVHD-induced experimental lupus nephritis model, and our study found the production of ANA and anti-dsDNA in the 1D1-treated group was lower than those in IgG-treated group after four weeks. The pathological injure of kidney in the 1D1-treated group was lighten than that in IgG-treated group.
Discussion and conclusions: Our data showed that blockade of CD86/CD28 with 1D1 induced a significant remission of proteinuria, production of autoantibodies, immune complex deposition and renal parenchyma lesions in experimental mice. Anti-CD86 Abs might be a potential method for immune therapy in autoimmune diseases and transplantation. 相似文献