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  • The American Association of Immunologists  (5)
  • 2020-2024  (5)
  • Medicine  (5)
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  • The American Association of Immunologists  (5)
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  • 2020-2024  (5)
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  • Medicine  (5)
RVK
  • 1
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 1_Supplement ( 2020-05-01), p. 150.6-150.6
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 150.6-150.6
    Abstract: Pregnancy is a significant immunological event, which has been shown to induce changes in maternal T cells. Studies examining maternal T cell responses in pregnancy have largely been conducted using mice that express transgenic “surrogate” fetal antigens, and have focused mainly on divided alloreactive T cells. Yet, maternal T cells may exhibit a broader range of responses during pregnancy some of which may not rely upon TCR signaling or cellular proliferation. To investigate the full spectrum of endogenous maternal T cell responses in natural pregnancy, we used the Nur77 mouse model, which allows for a graded assessment of TCR signaling using a GFP reporter. Splenocytes from female CD45.2 Nur77 mice were labeled with CellTrace Violet (CTV) to detect cellular division and transferred into female CD45.1 congenic mice. These host females were then mated with either syngeneic CD45.1 or allogeneic Balb/c males or left naive non-mated controls. Splenocytes were collected on either embryonic day 10 or 18 (E10 or E18) and analyzed using flow cytometry. t-SNE analysis revealed few phenotypic differences between the experimental groups at E10 with significantly increased separation by E18, which was most evident in the CD4 compartment. Interestingly, this separation was driven primarily by changes in the expression of selectins (i.e. downregulation of CD62L) and cytokine receptors (i.e. increased expression of CD25) as opposed to changes in TCR signaling (GFP) or cellular division (CTV). Accordingly, we conclude that maternal T cell responses in pregnancy are significantly shaped by non-antigen driven signals. The functional impact of these non-antigen driven changes in cellular phenotype are unknown and currently under investigation.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
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  • 2
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 206, No. 4 ( 2021-02-15), p. 919-919
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2021
    detail.hit.zdb_id: 1475085-5
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  • 3
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 205, No. 8 ( 2020-10-15), p. 2091-2099
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 205, No. 8 ( 2020-10-15), p. 2091-2099
    Abstract: Hepatitis C virus (HCV) infection is the cause of severe liver disease in many people. The restricted species tropism of HCV hinders the research and development of drugs and vaccines. The Chinese tree shrew (Tupaia belangeri chinensis) is a close relative of primates and can be infected by HCV, but the underlying mechanisms are unknown. In this study, we have characterized the functions of tree shrew MAVS (tMAVS) in response to HCV infection and defined the capacity of HCV replication. HCV was shown to be colocalized with tMAVS in primary tree shrew hepatocytes and cleaved tMAVS at site Cys508 via its NS3/4A protease, with a modulating effect by site Glu506 of tMAVS. The tMAVS cleavage by HCV NS3/4A impaired the IRF3-mediated induction of IFN-β but maintained the activated NF-κB signaling in the tree shrew primary cells. Activation of the tMAVS-dependent NF-κB signaling inversely inhibited HCV replication and might limit the establishment of persistent infection. Overall, our study has revealed an elegant example of the balance between the host defenses and HCV infection via the MAVS-mediated antiviral signaling and has provided an insight into the mechanisms underpinning HCV infection in the Chinese tree shrew.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    The American Association of Immunologists ; 2020
    In:  The Journal of Immunology Vol. 204, No. 1_Supplement ( 2020-05-01), p. 160.6-160.6
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 160.6-160.6
    Abstract: Parkinson’s disease is a complexly neuronal injury and accompanied by many clinical challenges, for example, lacking of early diagnostic strategies and effective treatment. Here, we demonstrate that in the subacute Parkinson’s disease mice model, injection of HMGB1 competitive inhibitor protein HMGB1 A Box restored the number of dopaminergic neurons and TH+ fibers in the substantia nigra striatum. Our data also showed that A Box inhibited the activation of microglia mediated by neuronal injury and the production of TNF α and IL-1β by up-regulating microglia CD200-CD200R signal axis in vitro and in vivo. Microglia overexpressing CD200R produced fewer inflammatory mediators and restored TH+ neurons in vitro. Intravenous injection of A Box also reduced the levels of RANTES and CXCL12 in substantia nigra and significantly inhibited Th17 cells infiltration. The ability of activated microglia to promote naïve CD4+ T cells differentiation into Th17 in MPP+ model in vitro was also inhibited by A Box. Elevated levels of these two chemokines were also detected in the serum of the patients. In conclusion, our studies show that HMGB1 can induce neuronal damage by activating microglia to promote the production of inflammatory mediators. HMGB1 itself does not directly cause neuronal death. Moreover, the differentiation of T cells into Th17 and migration of T cells secondary to microglia activation induced by HMGB1 further aggravates neuronal damage. The significant effect of HMGB1 A Box indicates the possibility that this recombinant protein might become a potent inhibitor of neuroinflammation in Parkinson’s disease.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2020
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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  • 5
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 206, No. 9 ( 2021-05-01), p. 2088-2100
    Abstract: Preserving appropriate function and metabolism in regulatory T (Treg) cells is crucial for controlling immune tolerance and inflammatory responses. Yet how Treg cells coordinate cellular metabolic programs to support their functional specification remains elusive. In this study, we report that BATF couples the TH2-suppressive function and triglyceride (TG) metabolism in Treg cells for controlling allergic airway inflammation and IgE responses. Mice with Treg-specific ablation of BATF developed an inflammatory disorder characterized by TH2-type dominant responses and were predisposed to house dust mite–induced airway inflammation. Loss of BATF enabled Treg cells to acquire TH2 cell–like characteristics. Moreover, BATF-deficient Treg cells displayed elevated levels of cellular TGs, and repressing or elevating TGs, respectively, restored or exacerbated their defects. Mechanistically, TCR/CD28 costimulation enhanced expression and function of BATF, which sustained IRF4 activity to preserve Treg cell functionality. Thus, our studies reveal that BATF links Treg cell functional specification and fitness of cellular TGs to control allergic responses, and suggest that therapeutic targeting of TG metabolism could be used for the treatment of allergic disease.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    RVK:
    RVK:
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2021
    detail.hit.zdb_id: 1475085-5
    Location Call Number Limitation Availability
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