Редактирование: CXCL16 (раздел)

==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
}}
{{medline-entry
|title=Estrogen receptor β, a regulator of androgen receptor signaling in the mouse ventral prostate.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28439009
|abstract=As estrogen receptor β  (ERβ ) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ  mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor ([[AR]]) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog ([[PTEN]]). ERβ agonist increased expression of the [[AR]] corepressor dachshund family (DACH1/2), T-cadherin, stromal caveolin-1, and nuclear [[PTEN]] and decreased expression of R[[AR]]-related orphan receptor c, Bcl2, inducible nitric oxide synthase, and IL-6. In the ERβ  mouse VP, RNA sequencing revealed that the following genes were up-regulated more than fivefold: Bcl2, clusterin, the cytokines [[CXCL16]] and -17, and a marker of basal/intermediate cells (prostate stem cell antigen) and cytokeratins 4, 5, and 17. The most down-regulated genes were the following: the antioxidant gene glutathione peroxidase 3; protease inhibitors WAP four-disulfide core domain 3 (WFDC3); the tumor-suppressive genes T-cadherin and caveolin-1; the regulator of transforming growth factor β signaling SMAD7; and the [[PTEN]] ubiquitin ligase [[NEDD4]]. The role of ERβ in opposing [[AR]] signaling, proliferation, and inflammation suggests that ERβ-selective agonists may be used to prevent progression of prostate cancer, prevent fibrosis and development of benign prostatic hyperplasia, and treat prostatitis.
|mesh-terms=* Aging
* Androgens
* Animals
* Chemokine CXCL16
* Chemokines, CXC
* Clusterin
* Down-Regulation
* Estrogen Receptor beta
* Interleukin-6
* Keratins
* Male
* Mice
* Mice, Knockout
* Nedd4 Ubiquitin Protein Ligases
* PTEN Phosphohydrolase
* Prostate
* Proto-Oncogene Proteins c-bcl-2
* Receptors, Androgen
* Signal Transduction
* Smad7 Protein
|keywords=* TGFβ
* cancer prevention
* inflammation
* nuclear receptor
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441728
}}
{{medline-entry
|title=Age-related alterations in blood and colonic dendritic cell properties.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26942871
|abstract=Dendritic cells (DC) determine initiation, type and location of immune responses and, in adults, show decreased Toll-like receptors and some increased cytokine levels on ageing. Few studies in children have characterised DC or explored DC-related mechanisms producing age-related immune changes. The pDC marker BDCA2 (but not CD123) was absent in pre-pubertal children and numbers of pDC decreased with age. Blood and colonic DC were more mature and activated in adults. Decrease in pDC numbers correlated with reduced GM-CSF levels with aging, but increasing IL-4 and IL-8 levels correlated with a more activated DC profile in blood. [[CXCL16]] levels decreased with age. Blood and colonic DC phenotypes were determined in healthy adults and children by flow cytometry and correlated with aging. Blood DC were divided into plasmacytoid (pDC) and myeloid (mDC) while only mDC were identified in colon. Serum cytokine levels were determined by multiplex cytokine assays and correlated with DC properties. In children, lack of BDCA2, a receptor mediating antigen capture and inhibiting interferon induction, may be immunologically beneficial during immune development. Conversely, reduced pDC numbers, probably secondary to decreasing GM-CSF and increasing cytokine-induced maturation of DC are likely to determine deteriorating immunity with ageing.
|mesh-terms=* Adult
* Age Factors
* Biomarkers
* Cell Differentiation
* Cells, Cultured
* Child
* Colon
* Cytokines
* Dendritic Cells
* Humans
* Myeloid Cells
|keywords=* BDCA-2
* Gerotarget
* aging
* children
* cytokines
* mDC
* pDC
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4914258
}}