Microbiology & Immunology - Theses

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Characterization of roles of IRF8 in dendritic cell development and function

Huang, Zhongyu ( 2018)

Dendritic cells (DC) are an essential component of immune system. Antigen presentation by DCs initiates T cell responses and builds up defense against pathogens. There are two major types of DC, conventional DCs (cDCs) and plasmacytoid DCs (pDCs), both of which derive from the same progenitor. The cDCs can be further classified by surface marker CD11b and CD8. While cDCs function as the major antigen presenting cells, pDCs are more efficient in type I IFN production. Regarding the functional difference, it is important to comprehend factors that control the production of these two types of DC. It has been reported that IRF8 mutation in human causes selective loss of DC subsets. Although IRF8 has been identified as key regulator in DC transcription network, study addressing the function of IRF8 in DC development and function remains incomplete. In this project, we show that the generation of pDCs and cDC1s depends largely but not entirely on IRF8. Upon germline deletion of IRF8, normal function of pDCs was disrupted while the antigen presentation of cDC1s was complemented by other mechanisms.