PT  - JOURNAL ARTICLE
AU  - TAKUYA GOTO
AU  - YOSHIYA ITO
AU  - NOBUYUKI NISHIZAWA
AU  - YU KURODA
AU  - SHUJI NAKAMOTO
AU  - KANAKO HOSONO
AU  - TAKESHI NAITOH
AU  - NAOKI HIKI
AU  - HIDEKI AMANO
TI  - Expansion of iNKT Cells Promotes Liver Repair Following Hepatic Ischemia Reperfusion Injury
AID  - 10.21873/invivo.12995
DP  - 2022 Nov 01
TA  - In Vivo
PG  - 2604--2614
VI  - 36
IP  - 6
4099  - http://iv.iiarjournals.org/content/36/6/2604.short
4100  - http://iv.iiarjournals.org/content/36/6/2604.full
SO  - In Vivo2022 Nov 01; 36
AB  - Background/Aim: Invariant natural killer T (iNKT) cells are involved in the initiation and resolution of inflammatory responses. We previously reported that activated iNKT cells facilitate liver repair after hepatic ischemia reperfusion (I/R) injury by accelerating macrophage polarization during the early phase of hepatic I/R injury. Upon activation with α-galactosylceramide (α-GalCer), iNKT cell numbers transiently decrease before increasing within 72 h of stimulation. In the present study, we examined the role of expanded hepatic iNKT cells in the late phase of hepatic I/R injury. Materials and Methods: iNKT cells were activated by intraperitoneal injection of α-GalCer in male C57/BL6 mice at the induction of hepatic ischemia followed by reperfusion. Results: Numbers of activated hepatic iNKT cells immediately diminished after hepatic I/R and reached minimal levels at 24 h and 48 h post-reperfusion. Numbers of hepatic iNKT cells then increased at 72 h and 96 h post-reperfusion to levels approximately 2-fold higher than in mice that underwent a sham operation. Liver repair as demonstrated by decreased necrotic area and increased expression of proliferating cell nuclear antigen (PCNA) was enhanced in α-GalCer-treated mice at 96 h post-reperfusion. Interleukin (IL)-13 production by proliferating iNKT cells was observed at 96 h post-reperfusion, which was associated with enhanced liver repair and increased numbers of reparative macrophages. Conclusion: Repopulation of hepatic iNKT cells promotes liver repair by stimulating macrophage phenotype switching in the late phase of hepatic I/R injury.