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CCR9 axis inhibition enhances hepatic migration of plasmacytoid DCs and protects against liver injury
Yuzo Koda, … , Michiie Sakamoto, Takanori Kanai
Yuzo Koda, … , Michiie Sakamoto, Takanori Kanai
Published August 9, 2022
Citation Information: JCI Insight. 2022;7(17):e159910. https://doi.org/10.1172/jci.insight.159910.
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Research Article Hepatology Immunology Article has an altmetric score of 3

CCR9 axis inhibition enhances hepatic migration of plasmacytoid DCs and protects against liver injury

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Abstract

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.

Authors

Yuzo Koda, Nobuhiro Nakamoto, Po-Sung Chu, Toshiaki Teratani, Akihisa Ueno, Takeru Amiya, Nobuhito Taniki, Sayako Chiba, Kentaro Miyamoto, Michiie Sakamoto, Takanori Kanai

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Figure 1

CCR9 deficiency induces hepatic pDC accumulation under steady-state conditions.

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CCR9 deficiency induces hepatic pDC accumulation under steady-state cond...
(A) Top: Representative B220 and PDCA-1 staining of CD45+CD11b–-gated BM, S-IE, and PB mononuclear cells (MNCs) in male WT or Ccr9–/– mice with C57BL/6 background. Bottom: Representative histograms showing CCR9 expression in hepatic CD45+CD11b–B220+PDCA-1+ pDCs. (B) Mean percentages of pDCs in the CD45+ MNC population from BM, S-IE, PB, and livers of WT or Ccr9–/– mice. Data represent the mean ± SEM (n = 7 per group). (C) Absolute numbers of pDCs in PB and liver. Data represent the mean ± SEM (n = 7 per group). **P < 0.01, Student’s t test. Data are combinations of 2 independent experiments from over 5 independent experiments (B and C).

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