TY - JOUR AU - Koda, Yuzo AU - Nakamoto, Nobuhiro AU - Chu, Po-Sung AU - Teratani, Toshiaki AU - Ueno, Akihisa AU - Amiya, Takeru AU - Taniki, Nobuhito AU - Chiba, Sayako AU - Miyamoto, Kentaro AU - Sakamoto, Michiie AU - Kanai, Takanori T1 - CCR9 axis inhibition enhances hepatic migration of plasmacytoid DCs and protects against liver injury PY - 2022/09/08/ AB - Plasmacytoid dendritic cells (pDCs) perform dual proinflammatory and immunosuppressive roles. We recently reported the potential of pDC therapy for treatment of intractable acute liver failure. However, establishment of efficient methods to deliver pDCs to the liver is essential for future clinical therapeutic applications. The present study demonstrates a higher abundance of liver and peripheral blood pDCs in mice lacking C-C motif chemokine receptor 9 (CCR9), a pDC gut-homing receptor, than in WT mice. Adoptive transfer of Ccr9–/– pDCs resulted in a higher efficiency of migration to the liver than WT pDCs did, while WT pDCs migrated efficiently to the original target organ, the small intestine. Further, Ccr9–/– pDCs consistently migrated efficiently to livers with concanavalin A–induced inflammation, and exerted a more effective immunosuppressive effect, resulting in better protection against acute liver inflammation than that demonstrated by WT pDCs. These findings highlight the therapeutic potential of the manipulation of the CCR9 axis as an approach to improve migration of immunosuppressive pDCs to the liver in order to exploit their beneficial effects in acute liver disease. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.159910 VL - 7 IS - 17 UR - https://doi.org/10.1172/jci.insight.159910 PB - The American Society for Clinical Investigation ER -