عنوان

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

شماره

TL3p05b6rj

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

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

نام عام مواد

[Thesis]

نام نخستين پديدآور

Kim, Jun Hwan

نام ساير پديدآوران

Raz, EyalZuniga, Elina

تاریخ نشرو بخش و غیره

2018

کسي که مدرک را اعطا کرده

Raz, EyalZuniga, Elina

امتياز متن

2018

متن يادداشت

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.

مستند نام اشخاص تاييد نشده

Pope, Herbert Lavar

مستند نام اشخاص تاييد نشده

Kim, Jun Hwan

مستند نام تنالگان تاييد نشده

UC San Diego

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y