Effects of Inflammatory Response on Dendritic Cell Development from CLPs
Date Issued
2014
Date
2014
Author(s)
Chao, Ying-Yin
Abstract
Toll-like receptors (TLRs) are one family of the pattern recognition receptors in the innate immunity to sense and response to microbial or viral infection. TLRs are expressed in innate immune cells, including macrophage and dendritic cells (DC) and non-immune cells such as epithelium in the gut and lung. Interestingly, TLRs also expressed in hematopoietic stem and progenitor cells (HSPCs). However, the roles of TLR response in HSPCs are largely unknown. We showed here that Flt3 ligand (FL) preferentially promoted pDC formation from common lymphoid progenitor (CLP), while TLR9 signaling promoted cDC differentiation. CpG ODN alone or CpG ODN plus FL, and not FL alone, also induced an unique DC population, which expressed both CD11b and B220 (double positive) other than CD11c. Interestingly, the morphology and phenotype of these DPDCs were more closer to those of cDCs and not to those of pDCs. The development of CpG-induced cDCs and DPDCs were not altered in the absence of STAT1, or IFNAR1, the type I interferon (IFN-I) receptor, suggesting that the process is IFN-I-independent. However, the effect of CpG ODN on DC development was dependent on direct TLR9 signaling pathway and not on TLR9-induced genes, as biased cDC development was impaired in Tlr9-/- CLPs when co-cultured with WT CLPs. Moreover, this effect was abolished in the absence of STAT3, suggesting that STAT3 might positively regulate TLR9-induced development of cDC and DPDC. These results suggest that inflammation-induced remodeling of DC population may provide a unique way for a rapid reaction of the innate immune system upon infection or inflammation.
Subjects
樹突細胞發育
發炎反應
淋巴共同前驅細胞
類鐸受體
活化訊號傳導與轉錄子三
Type
thesis
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