Modulace funkce plazmacytoidních dendritických buněk: role immunoreceptorů TIM-3 a BDCA-2
Autor: | Font Haro, Albert |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
HIV-1 restriction in pDCs
interferon typu I (IFN-I) plasmacytoid dendritic cells (pDCs) inhibitory kináz SYK a MEK-ERK Toll-like receptor 7 a 9 (TLR7 type I interferon (IFN-I) plasmacytoidní dendritické buňky (pDCs) regulačně inhibitory immunoreceptors BDCA-2 and TIM-3 viremic and aviremic HIV-1 infected individuals SYK and MEK-ERK kinase inhibitors viremičtí a neviremičtí pacienti infikovaní HIV-1 TLR9) HIV-1 restrikce HIV-1 v pDCs strategies for anti-HIV-1 therapy regulatory strategie antiretrovirové terapie inhibiční imunoreceptory BDCA-2 a TIM-3 Toll-like receptor 7 and 9 (TLR7 |
Druh dokumentu: | Doctoral Thesis |
Popis: | Albert Font Haro ABSTRACT Modulation of plasmacytoid dendritic cell function: role of immunoreceptors TIM-3 and BDCA-2 Plasmacytoid dendritic cells (pDCs) are key players in the antiviral response as well as in linking innate and adaptive immune response. They express endosomal toll-like receptors 7 and 9, which can detect ssRNA and unmethylated CpG DNA, respectively. Due to the constitutive expression of the transcription factor IRF7, pDCs are able to rapidly produce massive quantities of type I (α, β, ω) and type III (1, 2, 3, 4) interferons (IFN-I and IFN-III) as well as pro- inflammatory cytokines such as IL-1, IL-6 and TNF-α. After maturation, they also function as antigen-presenting cells. Despite intense research, the mechanisms of IFN and pro-inflammatory cytokines production and regulation are still poorly understood. Using the pDC cell line GEN2.2 and also primary human pDCs, we shed light on the role of kinases MEK and SYK in IFN-I production and regulation. We found that SYK is not only involved in the regulatory receptor (RR)-mediated BCR-like pathway that represents the negative regulation of IFN-I and IFN-III secretion but also in the positive TLR7/9-mediated signal transduction pathway that leads to IFN-I production, representing the immunogenic function. We also found that MEK plays a... |
Databáze: | Networked Digital Library of Theses & Dissertations |
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