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Hausding M Karwot R Scholtes P Lehr HA Wegmann M Renz H Galle PR Birkenbach M Neurath MF Blumberg RS Finotto S 《European journal of immunology》2007,37(6):1663-1677
Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3-/- mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1+ cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c+ cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD11c+ cells isolated from EBI-3-/- mice express markers of a more plasmacytoid phenotype without releasing IFN-alpha as compared to those from wild-type littermates. Moreover, allergen challenge induced the development of myeloid CD11c+ cells in the lungs of EBI-3-/- mice, which released increased amounts of IL-10 and IL-12 while not expressing IFN-alpha. Finally, inhibition of EBI-3 expression in lung DC could prevent AHR in adoptive transfer studies by suppressing mediator release of effector cells into the airways. These results indicate a novel role for EBI-3 in controlling local immune responses in the lungs in experimental asthma. 相似文献
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Fei Ma Mingning Zhao Zhenyu Song Zhongchuan Wang 《Clinical and experimental pharmacology & physiology》2019,46(9):798-805
Pathogenic inflammation mediated by overactive type 1 helper T cell (Th1) responses could exacerbate and perpetuate Crohn's disease. Programmed death (PD)‐1 and its ligand PD‐L1 pathway could be upregulated to suppress inflammation. We wondered why this pathway is ineffective at suppressing pathogenic Th1 inflammation in Crohn's disease patients. Here, we found that overexpression of T‐bet via transfection significantly reduced the expression of PD‐1. PD‐L1 was capable of suppression proinflammatory CD4+ T cells, but T‐bet transfection significantly reduced the susceptibility of CD4+ T cells toward PD‐L1‐mediated suppression, evidenced by the observations that at low PD‐L1 concentration T‐bet transfected and mock transfected CD4+ T cells presented comparable IL‐2 production, but at high PD‐L1 concentration, T‐bet transfected CD4+ T cells presented significantly higher IL‐2 than mock transfected CD4+ T cells. PD‐L1 could significantly reduce the survival of CD4+ T cells from Crohn's disease patients, but interestingly, in the absence of PD‐L1, the survival was better in mock transfected CD4+ T cells, while in the presence of PD‐L1, the survival was better in T‐bet transfected CD4+ T cells. Crohn's disease patients with greater severity presented higher T‐bet expression and lower PD‐1 expression in CD4+ T cells, demonstrating an association between T‐bet expression and disease progression. We also discovered that stimulation with bacterial antigens could upregulate the expression of T‐bet. Together, this study demonstrated that T‐bet overexpression could interfere with PD‐1/PD‐L1‐mediated suppression of CD4+ T cell inflammation and survival, and potentially contributed to the development and persistence of Crohn's disease. 相似文献
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Bobat S Flores-Langarica A Hitchcock J Marshall JL Kingsley RA Goodall M Gil-Cruz C Serre K Leyton DL Letran SE Gaspal F Chester R Chamberlain JL Dougan G López-Macías C Henderson IR Alexander J MacLennan IC Cunningham AF 《European journal of immunology》2011,41(6):1606-1618
Clearance of disseminated Salmonella infection requires bacterial-specific Th1 cells and IFN-γ production, and Th1-promoting vaccines are likely to help control these infections. Consequently, vaccine design has focused on developing Th1-polarizing adjuvants or Ag that naturally induce Th1 responses. In this study, we show that, in mice, immunization with soluble, recombinant FliC protein flagellin (sFliC) induces Th2 responses as evidenced by Ag-specific GATA-3, IL-4 mRNA, and protein induction in CD62L(lo) CD4(+) T cells without associated IFN-γ production. Despite these Th2 features, sFliC immunization can enhance the development of protective Th1 immunity during subsequent Salmonella infection in an Ab-independent, T-cell-dependent manner. Salmonella infection in sFliC-immunized mice resulted in augmented Th1 responses, with greater bacterial clearance and increased numbers of IFN-γ-producing CD4(+) T cells, despite the early induction of Th2 features to sFliC. The augmented Th1 immunity after sFliC immunization was regulated by T-bet although T-bet is dispensable for primary responses to sFliC. These findings show that there can be flexibility in T-cell responses to some subunit vaccines. These vaccines may induce Th2-type immunity during primary immunization yet promote Th1-dependent responses during later infection. This suggests that designing Th1-inducing subunit vaccines may not always be necessary since this can occur naturally during subsequent infection. 相似文献
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Sascha Cording Jasna Medvedovic Emelyne Lécuyer Tegest Aychek François Déjardin Gérard Eberl 《European journal of immunology》2018,48(8):1271-1280
Natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were discovered more than 40 and 20 years ago, respectively. These two cell types were initially studied for their unique functions in the elimination of infected or transformed cells, and in the development of lymphoid tissues. It took an additional 10 years to realize that NK cells and LTi cells were members of a larger family of innate lymphoid cells (ILCs), whose phenotypes and functions mirror those of T cells. Many mouse models have since been developed to identify and isolate ILCs, map their developmental pathways and characterize their functions. Because of the similarity between ILCs and T cells, this exploration remains a challenge. In spite of this, a broad range of mouse models available to researchers has lead to significant progress in untangling the unique roles of ILCs early in defense, regulation of adaptive immunity and homeostasis. Here, we review these mouse models, and discuss their strengths and limitations. 相似文献
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Effect of calcium and vitamin D on growth,rickets and Kashin–Beck disease in 0‐ to 5‐year‐old children in a rural area of central Tibet 下载免费PDF全文
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