Thesis or Dissertation Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation

Arimura, Keiichi  ,  Takagi, H  ,  Uto, T  ,  Fukaya, T  ,  Nakamura, T  ,  Choijookhuu, N  ,  Hishikawa, Y  ,  Yamashita, Y  ,  Sato, K

2017-07 , Nature
ISSN:19330219
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学位論文の一部を構成しているため、http://hdl.handle.net/10458/6035 に本文を掲載。
Disruption of intestinal homeostasis can lead to inflammatory bowel diseases endowed susceptibility genes and environmental factors affecting intestinal accumulation and activation of colitogenic phagocytes. Plasmacytoid dendritic cells (pDCs) are immune cells that had been proposed to control innate and adaptive immunity through the massive secretion of type I interferon (IFN-I). However, the contribution of pDCs to the progression of intestinal inflammation remains unclear. Here we show a critical role of pDCs in the initiation of acute colonic inflammation using T-cell-independent acute colitis model with a selective ablation of pDCs. Although pDCs accumulated in the inflamed colon upon mucosal injury, deficiency of pDCs attenuated the development of acute colitis independent of IFN-I signaling, accompanied by the diminished colonic production of proinflammatory cytokines. Furthermore, deficiency of pDCs impaired the mobilization of colitogenic phagocytes into the inflamed colon possibly mediated by the abrogated mucosal production of C–C chemokine receptor 2 ligand. Thus, our findings highlight a critical role of pDCs in the induction of the colonic inflammation that regulates the colonic accumulation of inflammatory phagocytes leading to the initiation and exacerbation of acute colitis, and they may serve a key role in controlling gut mucosal immune homeostasis.

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