The Role of Type I Interferon in Regulating Development and functions of Plasmacytoid Dendritic Cell Subsets

• Main Authors: Wan-Jung Wu, 吳宛蓉
• Other Authors: Chien-Kuo Lee
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/29619070671043306950

碩士 === 國立臺灣大學 === 免疫學研究所 === 101 === Dendritic cells are professional antigen presenting cells which connect innate and adaptive immune system throughout lymphoid organs. Conventional DC and plasmacytoid DC are the two major DC populations, which can be generated from both myeloid progenitors, such as macrophage DC progenitor and common DC progenitor (CDP), and lymphoid progenitors, such as common lymphoid progenitor (CLP). pDCs are known for their ability to produce robust amount of IFN-I during virus infection. However, it is still not completely understood how IFN-I regulates pDC subsets development and functions. Ex vivo functional assay showed that Ifnar1-/- pDC expressed lower level of CD86, and produced less proinflammatory cytokines and IFN-I than did WT pDC in response to a TLR9 ligand. In addition, Stat1-/- and Stat2m/m pDC also displayed impaired functions, which is consistent with Ifnar1-/- pDC. Interestingly, the amount of CD4+CD8+ and CD4+CD8- pDCs, two subsets of pDCs, was significantly diminished in Ifnar1-/- BM and spleen. Moreover, production of IL-6 and IFN-I were reduced in Ifnar1-/- pDC subsets upon CpG ODN stimulation. Among 4 different pDC subsets, CD4-CD8- pDC express the highest levels of MHC-II and CD86, and produce the greatest amount of IL-6 in response to CpG stimulation, compared to the other three subsets. In vitro BM culture showed that Ifnar1-/- BM developed fewer pDC and the impaired pDC development and functions in the absence of IFNAR1 could not be rescued supplemented with high dose FL. Taken together, IFN-I play a positive role in regulating pDC functions via STAT1 and STAT2 pathway, and CD4-CD8- pDCs are more activated and may represent the most mature population of pDCs after CpG stimulation.