عنوان

cAMP in dendritic cell alters the fate of Th2 and Th17 responses

Number

TL3p05b6rj

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

cAMP in dendritic cell alters the fate of Th2 and Th17 responses

General Material Designation

[Thesis]

First Statement of Responsibility

Kim, Jun Hwan

Subsequent Statement of Responsibility

Raz, EyalZuniga, Elina

Date of Publication, Distribution, etc.

2018

Body granting the degree

Raz, EyalZuniga, Elina

Text preceding or following the note

2018

Text of Note

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.

Pope, Herbert Lavar

Kim, Jun Hwan

UC San Diego

Electronic name

p

[Thesis]

276903

a

Y