Редактирование: CXCR6

C-X-C chemokine receptor type 6 (CXC-R6) (CXCR-6) (CDw186) (G-protein coupled receptor STRL33) (G-protein coupled receptor bonzo) (CD186 antigen) [BONZO] [STRL33] [TYMSTR]

==Publications==

{{medline-entry
|title=[[CXCR6]] Inhibits Hepatocarcinogenesis by Promoting Natural Killer T- and [[CD4]]  T-Cell-Dependent Control of Senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30710528
|abstract=Inflammation in the liver provokes fibrosis, but inflammation is also important for tumor surveillance. Inhibitors of chemokine pathways, such as [[CXCL16]] and [[CXCR6]] regulation of lymphocyte trafficking, are being tested as antifibrotic agents, but their effects on the development of hepatocellular carcinoma (HCC) are unclear. We assessed the roles of [[CXCR6]]-dependent immune mechanisms in hepatocarcinogenesis. C57BL/6J wild-type (WT) mice and [[CXCR6]]-deficient mice (Cxcr6 ) were given injections of diethylnitrosamine (DEN) to induce liver cancer and α-galactosylceramide to activate natural killer T (NKT) cells. We also performed studies in mice with conditional, hepatocyte-specific deletion of NEMO, which develop inflammation-associated liver tumors (Nemo  and Nemo Cxcr6  mice). We collected liver tissues from patients with cirrhosis (n = 43), HCC (n = 35), and neither of these diseases (control individuals, n = 25). Human and mouse liver tissues were analyzed by histology, immunohistochemistry, flow cytometry, RNA expression arrays (from sorted hepatic lymphocytes), and matrix-assisted laser desorption/ionization imaging. Bone marrow was transferred from Cxcr6  or WT mice to irradiated C57BL/6J mice, and spleen and liver cells were analyzed by flow cytometry. [[CD4]]  T cells or NKT cells were isolated from the spleen and liver of [[CD4]]5.1  WT mice and transferred into [[CXCR6]]-deficient mice after DEN injection. After DEN injection, [[CXCR6]]-deficient mice had a significantly higher tumor burden than WT mice and increased tumor progression, characterized by reduced intrahepatic numbers of invariant NKT and [[CD4]]  T cells that express tumor necrosis factor and interferon gamma. Livers of Nemo Cxcr6  mice had significantly more senescent hepatocytes than livers of Nemo  mice. In studies of bone-marrow chimeras, adoptive cell transfer experiments, and analyses of Nemo  mice, we found that NKT and [[CD4]] T cells promote the removal of senescent hepatocytes to prevent hepatocarcinogenesis, and that this process required [[CXCR6]]. Injection of WT with α-galactosylceramide increased removal of senescent hepatocytes by NKT cells. We observed peritumoral accumulation of [[CXCR6]]-associated lymphocytes in human HCC, which appeared reduced compared with cirrhosis tissues. In studies of mice with liver tumors, we found that [[CXCR6]] mediated NKT-cell and [[CD4]]  T-cell removal of senescent hepatocytes. Antifibrotic strategies to reduce [[CXCR6]] activity in liver, or to reduce inflammation or modulate the immune response, should be tested for their effects on hepatocarcinogenesis.
|mesh-terms=* Animals
* CD4-Positive T-Lymphocytes
* Carcinogenesis
* Carcinoma, Hepatocellular
* Cellular Senescence
* Diethylnitrosamine
* Disease Progression
* Galactosylceramides
* Hepatocytes
* Humans
* Immunologic Surveillance
* Interferon-gamma
* Intracellular Signaling Peptides and Proteins
* Liver Cirrhosis
* Liver Neoplasms
* Lymphocyte Activation
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Knockout
* Natural Killer T-Cells
* Receptors, CXCR6
* Tumor Burden
* Tumor Necrosis Factor-alpha
|keywords=* Chemokine
* Liver Cancer
* NKT Cells
* Senescence
|full-text-url=https://sci-hub.do/10.1053/j.gastro.2019.01.247
}}