Flt3 受器下游訊息傳導分子影響樹突細胞發育的研究

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in controlling the immune responses. DCs can be roughly classified into two subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs half-life is short and required continuously generated from their progenitors. DCs origin from both myeloid and lymphoid progenitors. In hematopoietic stage, the CMP in myloid lineage and CLP in lymphoid lineage are developmentaly equivalent. We first demostrated that the CLP have the highest pDC potential compared to other myelopid progenitors, including CMP and two subsets of CDPs. The development of DCs is highly dependent on Flt3 signaling. However, little is known about how Flt3 signaling involved in the decision of becoming cDCs or pDCs during development. In this study, we identified p38, a member of MAPK, are essential for pDCs development. Inhibitor targeting p38 show reduction of pDCs percentage and number but promote cDCs development from primary progenitors in vitro. Similar effects also were observed in iHSPC cell line with loss-of-function treatment, including inhibitors and knockdown approach, these treatments delay DC development. Moreover, the progeny cell number increased in the absent of p38. Together, we identified that p38 play a critical role in DC development and also DC subset determination that p38 act as positive regulator in pDC but negatively regulate cDC population