title: Role of hepatocyte-derived IL-7 in maintenance of intrahepatic NKT cells and T cells and development of B cells in fetal liver.
abstract: The liver contains a variety of resident immune cells, such as NK cells, NKT cells, T cells, macrophages, and dendritic cells. However, little is known about how IL-7, which is produced by hepatocytes, functions locally in development and maintenance of liver immune cells. To address this question, we established IL-7-floxed mice and crossed them with albumin promoter-driven Cre (Alb-Cre) transgenic mice to establish conditional knockout of IL-7 in hepatocytes. The levels of IL-7 transcripts were reduced 10-fold in hepatocyte fraction. We found that the absolute numbers of NKT and T cells were significantly decreased in adult liver of IL-7(f/f) Alb-Cre mice compared with IL-7(f/f) control mice. In contrast, NK cells, dendritic cells, and B cells were unchanged in the IL-7(f/f) Alb-Cre liver. The number of Vα14(+) invariant NKT cells was significantly reduced in liver, but not in thymus and spleen, of IL-7(f/f) Alb-Cre mice. Furthermore, B cell development was impaired in perinatal liver of IL-7(f/f) Alb-Cre mice. This study demonstrates that hepatocyte-derived IL-7 plays an indispensable role in maintenance of NKT and T cells in adult liver and development of B cells in fetal liver, and suggests that hepatocytes provide a unique IL-7 niche for intrahepatic lymphocytes.
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Bingfei
authors.initials: B
authors.lastname: Liang
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wagatsuma
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.forename: Kazushige
authors.initials: K
authors.lastname: Maki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Miyachi
authors.forename: Satsuki
authors.initials: S
authors.lastname: Kitano
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yabe-Nishimura
authors.forename: Shizue
authors.initials: S
authors.lastname: Tani-Ichi
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D005333:Fetus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism; D015851:Interleukin-7 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D015851:Interleukin-7; C576410:interleukin-7, mouse