IL-2 and IL-12 Alter NK Cell Responsiveness to IFN-γ-Inducible Protein 10 by Down-Regulating CXCR3 Expression

Hodge, Deborah L.; Schill, William B.; Wang, Ji Ming; Blanca, Isaac; Reynolds, Della; Ortaldo, John R.; Young, Howard A.

doi:10.4049/jimmunol.168.12.6090

Cited by 63 publications

(47 citation statements)

References 37 publications

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“…Role of CCR2 in lung NK cell influx and outcome of infection. Because CCR2, the only known signaling receptor for MCP-1/CCL2, is expressed on NK cells (34)(35)(36)(37)(38)(39), we sought to corroborate our findings by examining the role of CCR2 on the recruitment of NK cells to the lung in this infection. We first injected CFSE-labeled NK cells from either WT or CCR2 -/-animals into neutrophil-depleted WT or CCR2 -/-mice before inoculation with A. fumigatus (Figure 6a).…”

Section: Effect Of Neutralization Of Mcp-1/ccl2 On the Influx Of Leukmentioning

confidence: 75%

Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Morrison

Park²,

Mooney³

et al. 2003

J. Clin. Invest.

190

143

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Section: Effect Of Neutralization Of Mcp-1/ccl2 On the Influx Of Leukmentioning

confidence: 75%

Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Morrison

Park²,

Mooney³

et al. 2003

J. Clin. Invest.

190

143

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“…Microarray experiments have been carried out on various immune cell subsets by a number of different investigators in order to understand gene expression differences during differentiation and activation. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] These studies have provided invaluable insight into comprehensive gene expression profiles that define many different immune cell subsets and states of differentiation and activation. In particular, a recent study detailed elegantly the genes expressed specifically in many subsets of the T-cell lineage.…”

Section: Introductionmentioning

confidence: 99%

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

Abbas¹,

Baldwin²,

Ma³

et al. 2005

Genes Immun

364

356

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Immune cell-specific expression is one indication of the importance of a gene's role in the immune response. We have compiled a compendium of microarray expression data for virtually all human genes from six key immune cell types and their activated and differentiated states. Immune Response In Silico (IRIS) is a collection of genes that have been selected for specific expression in immune cells. The expression pattern of IRIS genes recapitulates the phylogeny of immune cells in terms of the lineages of their differentiation. Gene Ontology assignments for IRIS genes reveal significant involvement in inflammation and immunity. Genes encoding CD antigens, cytokines, integrins and many other gene families playing key roles in the immune response are highly represented. IRIS also includes proteins of unknown function and expressed sequence tags that may not represent genes. The predicted cellular localization of IRIS proteins is evenly distributed between cell surface and intracellular compartments, indicating that immune specificity is important at many points in the signaling pathways of the immune response. IRIS provides a resource for further investigation into the function of the immune system and immune diseases.

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“…IL-2 augments mRNA expression and synthesis of IFN-␥ in NK cells. 11 Resting NK cells respond directly to IL-2 with enhanced cytotoxic activity in the absence of other stimuli. Long-term culture of NK cells with high-dose IL-2 leads to the generation of cells with a broad range of tumor target cell cytolytic capabilities.…”

Section: Biologic Functions Of Nk Cells Can Be Repressed By 15d-pgj 2mentioning

confidence: 99%

“…Interleukin-2 (IL-2) enhances intrinsic killing activity of NK cells and also induces a rapid expression of IFN-␥. 11 In contrast, interleukin-4 (IL-4) inhibits IFN-␥ production by human NK cells and regulates growth factor-dependent proliferation and differentiation of these cells. [12][13][14] Additionally, prostaglandins have been shown to inhibit NK cell cytolytic activity.…”

Section: Introductionmentioning

confidence: 99%

“…The ribonuclease protection assay including the labeling of probe, hybridization, RNAase digestion, and denaturing polyacrylamide gel electrophoresis was performed as previously described. 11 One microgram of isolated RNA was utilized for cDNA synthesis by ThermoScript reverse transcriptase-polymerase chain reaction (RT-PCR) system (Invitrogen). Platinum PCR Supermix (Invitrogen) was used for semiquantitative RT-PCR at a TouchDown Thermal Cycling System (Thermo-Hybaid, Franklin, MA).…”

mentioning

confidence: 99%

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Peroxisome proliferator-activated receptor-γ and its ligands attenuate biologic functions of human natural killer cells

Zhang

Rodríguez-Galán

Subleski

et al. 2004

Blood

Self Cite

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Interferon-␥ (IFN-␥) production and cytolytic activity are 2 major biologic functions of natural killer (NK) cells that are important for innate immunity. We demonstrate here that these functions are compromised in human NK cells treated with peroxisome proliferator-activated-␥ (PPAR-␥) ligands via both PPAR-␥-dependent and -independent pathways due to variation in PPAR-␥ expression. In PPAR-␥-null NK cells, 15-deoxy-⌬ 12,14 prostaglandin J 2 (15d-PGJ 2 ), a natural PPAR-␥ ligand, reduces IFN-␥ production that can be reversed by MG132 and/or chloroquine, and it inhibits cytolytic activity of NK cells through reduction of both conjugate formation and CD69 expression. In PPAR␥-positive NK cells, PPAR-␥ activation by 15d-PGJ 2 and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-␥. Overexpression of PPAR-␥ in PPAR-␥-null NK cells reduces IFN-␥ gene expression. However, PPAR-␥ expression and activation has no effect on NK cell cytolytic activity. In addition, 15d-PGJ 2 but not ciglitazone reduces expression of CD69 in human NK cells, whereas CD44 expression is not affected. These results reveal novel pathways regulating NK cell biologic functions and provide a basis for the design of therapeutic agents that can regulate the function of NK cells within the innate immune response. IntroductionNatural killer (NK) cells are bone marrow-derived cytotoxic lymphocytes with a granular morphology and account for up to 15% of peripheral blood lymphocytes. 1,2 They are important cellular components of innate immune defense against infection and immune surveillance against malignancies and transplanted organs. 3,4 NK cells are also implicated in the regulation of hematopoiesis and adaptive immune responses. 2,5 The biologic activity of NK cells includes not only cytokine production (eg, interferon-␥ [IFN-␥]) to regulate the type 1 T-cell immune response but also cytolytic activity, because NK cells can destroy target cells prior to sensitization and without restriction by major histocompatibility complex (MHC) antigens (natural killing activity). Imbalance of NK biologic functions has been implicated in the pathogenesis of autoimmune diseases such as diabetes. 6 Removal of NK cells abrogates cyclophosphamide-induced diabetes in nonobese diabetic (NOD) mice and prevents streptozotocin-induced diabetes in CD-1 mice. 7,8 Furthermore, IFN-␥ promotes the penetration of diabetogenic cells into pancreatic islets, and depletion of IFN-␥ delays the development of autoimmune diabetes in NOD mice. 9,10 Whereas the role of NK cells in pathogenesis has been extensively studied, the mechanisms involved in the regulation of NK functions remain to be defined. Many agents like cytokines, prostaglandins, and drugs regulate NK cell function. Interleukin-2 (IL-2) enhances intrinsic killing activity of NK cells and also induces a rapid expression of In contrast, interleukin-4 (IL-4) inhibits IFN-␥ production by human NK cells and regulates growth factor-dependent proliferation and differentiation of thes...

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IL-2 and IL-12 Alter NK Cell Responsiveness to IFN-γ-Inducible Protein 10 by Down-Regulating CXCR3 Expression

Cited by 63 publications

References 37 publications

Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis

Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data

Peroxisome proliferator-activated receptor-γ and its ligands attenuate biologic functions of human natural killer cells

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