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" cAMP in dendritic cell alters the fate of Th2 and Th17 responses "
Kim, Jun Hwan
Raz, EyalZuniga, Elina
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Latin Dissertation
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English
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| Record Number
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897866
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TL3p05b6rj
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| Main Entry
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Pope, Herbert Lavar
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| Title & Author
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cAMP in dendritic cell alters the fate of Th2 and Th17 responses\ Kim, Jun HwanRaz, EyalZuniga, Elina
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| Date
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2018
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2018
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| Abstract
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Dendritic cells are professional antigen presenting cells that activate naïve T cell to promote specific T cell responses. Until recently, the DCs’ recognition of microbial or inflammatory stimuli through PRRs was solely recognized to initiate DCs’ maturation. On the other hand, the role of PRR-independent activation of DCs has remained largely unexplored. This thesis will focus on a recent discovery of cAMP dependent DCs’ maturation. We treated various types of DCs with GPCR ligands and other regulators affecting GPCR/cAMP pathway. Here, we show that DCs’ varying levels of cAMP determine DCs’ ability to promote either Th2 responses or Th17 responses. We discovered that the increased cAMP level reduced the expression of DC’s transcription factors like IRF4 and KLF4. Subsequently, DC’s increased cAMP level reduced Th2 responses and increased Th17 responses. In fact, this cAMP dependent DC maturation is so robust that inducing cAMP signaling alone allowed Th2-promoting DC to switch into Th17-promoting DC. Surprisingly, we discovered that DC’s expression of IRF5 and inhibition of IRF4 are essential in Th17 polarization. In addition, we also described the implication of GPCR/cAMP pathway’s role in the onset of neutrophilic asthma. Th2 response in the airway is known to promote eosinophilic asthma while additional Th17 response induce neutrophilic asthma. Here, we show that a long-term exposure to asthma’s common bronchodilator, LABA, also switches Th2 mediated eosinophilic asthma into Th17 mediated neutrophilic asthma by elevating DC’s cAMP level. These findings delineate an unforeseen contribution of cAMP signaling in the regulation of innate and adaptive immunity.
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Kim, Jun Hwan
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UC San Diego
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