Z Gastroenterol 2020; 58(01): e38
DOI: 10.1055/s-0039-3402202
Lectures Session V Viral Hepatitis and Immunology: Saturday, February 15, 2020, 11:45 am – 12:30 pm, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

NK cells regulate LSEC to promote the HBV-specific T cells response

Y Du
1   University Hospital Essen, Department of Gastroenterology and Hepatology, Essen, Germany
2   Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Infectious Diseases, Wuhan, China
,
S Zou
2   Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Infectious Diseases, Wuhan, China
,
T Khera
1   University Hospital Essen, Department of Gastroenterology and Hepatology, Essen, Germany
,
E Littwitz Salomon
3   University Hospital Essen, Institute of Virology, Essen, Germany
,
M Han
2   Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Infectious Diseases, Wuhan, China
,
J Li
2   Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Infectious Diseases, Wuhan, China
,
U Dittmer
3   University Hospital Essen, Institute of Virology, Essen, Germany
,
M Lu
3   University Hospital Essen, Institute of Virology, Essen, Germany
,
D Yang
2   Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Infectious Diseases, Wuhan, China
,
H Wedemeyer
1   University Hospital Essen, Department of Gastroenterology and Hepatology, Essen, Germany
,
J Wu
2   Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Department of Infectious Diseases, Wuhan, China
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

 

Introduction:

It is unclear whether NK cells could regulate the function of liver sinusoidal endothelial cells (LSECs). Our previous study have indicated that activation of NOD1 signaling in the liver could enhance T cell response in a LSEC dependent manner and promote the recruitment and activation of NK cells in liver. Therefore, we hypothesized that the maturation of LSEC was dependent on NK cells.

Objectives:

Exploring whether intrahepatic NK cells could regulate the maturation of LSECs, and its effects and mechanism on HBV-specific T cells response.

Materials & methods:

The chronic HBV replication model was established by hydrodynamic injection (HI) of pAAV/HBV1.2 plasmid to male C57B6/L, CXCR3-/- or Rag1-/- mice. NOD1 ligand (diaminopimelic acid, DAP) was injected to mice by the same way. NK cells depletion was achieved by administration of anti- asialo-GM1. Purified intrahepatic NK cells and LSECs were cocultured at a 1:5 ratio with or without DAP presence. The phenotype of LSECs and HBV specific T cell response were detected by FACS.

Results:

  1. NK cells depletion significantly downregulated the costimulatory molecules and adhesion molecules on LSEC while upregulated the inhibitory molecule; thus impaired the maturation of LSEC function and the anti-HBV effect of DAP.

  2. Transfer CD8+T cells into NK cells depleted Rag-/- mice can"t restore the anti-HBV effects.

  3. cNK cells were recruited into liver and secreted more IFN-γ comparing the NS control after the treatment of DAP.

  4. NK cells was recruited into liver through CXCR3 axis and the anti-HBV effects of DAP also depended on this axis.

  5. Intrahepatic NK cells purified from naïve mice promoted the maturation of LSEC function, while NK cells from HBV mice impaired its effect in vitro, indicating that HBV impaired NK cells function.

  6. NK cells promote LSEC maturation through both soluble cytokines and direct contact.

Conclusion:

We demonstrated a crucial role of NK cells for LSEC maturation and activation as well as HBV-specific T cells response during DAP treatment in CHB mice.