IFN-γ-Dependent Recruitment of Mature CD27high NK Cells to Lymph Nodes Primed by Dendritic Cells

Watt, Sally V.; Andrews, Daniel M.; Takeda, Kazuyoshi; Smyth, Mark J.; Hayakawa, Yoshihiro

doi:10.4049/jimmunol.181.8.5323

Cited by 60 publications

(78 citation statements)

References 39 publications

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“…However, fewer CD11b lo CD27 hi NK cells were observed in the peritoneal cavity after inoculation with CpG-stimulated pDC (data not shown), in line with the observations of Watt et al [6], who described that the CD11b lo CD27 hi NK-cell population decreased in the LN of mice receiving LPS-stimulated mDC. For the rest of the present studies, Flt3L bone marrow-derived pDC were used to examine the mechanisms of pDC-induced recruitment of NK cells.…”

Section: Resultssupporting

confidence: 80%

“…Because of the interest in the role of NK cells in host responses to infections and tumors as well as for protective therapeutic strategies, it is of importance to understand more of the cellular and molecular requirements of NKcell activation in vivo. Previous studies investigating DC-induced NK-cell migration and activation in vivo have examined primarily CD11c 1 DC of myeloid origin generated from bone marrow cultures in GM-CSF (myeloid DC, mDC) [4,6,47]. However, there is little data on pDC-induced migration and subsequent activation of NK cells in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…The latter contribute to the immunoregulatory properties of NK cells, which affect anti-microbial and anti-tumor responses as well as the outcome of many autoimmune and hypersensitivity reactions [3]. By their cytotoxicity and cytokine production, NK cells can affect CTL responses in infection and tumor models as well as B-cell responses [4][5][6][7][8]. NK cells are found in both nonlymphoid and lymphoid tissues including lung, liver, blood, spleen, and LN [9].…”

Section: Introductionmentioning

confidence: 99%

“…NK cells can interact, directly or indirectly, with DC [4,5,[36][37][38][39][40][41][42][43][44][45]. For example, the activation of DC by pathogens leads to cytokine secretion, which activates NK cells, which in turn may affect the subsequent adaptive immune responses, either via cytokines or by direct cell-cell contact [5,6,46]. Because of the interest in the role of NK cells in host responses to infections and tumors as well as for protective therapeutic strategies, it is of importance to understand more of the cellular and molecular requirements of NKcell activation in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Plasmacytoid dendritic cell‐induced migration and activation of NK cells in vivo

Persson

Chambers

2010

Eur J Immunol

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NK cells are cytotoxic cells of the innate immune system. They have been found to be critical in the defense against infections and also against some tumors. Recent studies have shown that NK cells require signals from accessory cells to induce their recruitment and activation at the site of infection or tumor growth. In this study, we examined whether plasmacytoid DC (pDC) could recruit and activate NK cells in vivo. When CpG-stimulated pDC were injected i.p. to C57BL/6 mice, they efficiently recruited NK cells, a process that was dependent on NK cell CXCR3 and CD62L and in part on CCR5. NK cells isolated from the peritoneum of mice inoculated with TLR7/8 or TLR9-stimulated pDC exhibited greater cytotoxicity against YAC-1 tumor cells than NK cells recovered from mice inoculated with control pDC. The present results are discussed in relation to pDC-induced NK cell migration and activation in vivo.Key words: Cellular activation . Cell migration . Costimulatory moleculers . Dendritic cells . NK cell IntroductionNK cells are lymphocytes of the innate immune system that play a crucial role in the early host defense against infections and some tumors [1]. NK cells have potent cytotoxic functions and are efficient producers of several cytokines including IFN-g, TNF-a, and GM-CSF [2]. The latter contribute to the immunoregulatory properties of NK cells, which affect anti-microbial and anti-tumor responses as well as the outcome of many autoimmune and hypersensitivity reactions [3]. By their cytotoxicity and cytokine production, NK cells can affect CTL responses in infection and tumor models as well as B-cell responses [4][5][6][7][8]. NK cells are found in both nonlymphoid and lymphoid tissues including lung, liver, blood, spleen, and LN [9]. Several studies have demonstrated that NK cells migrate to different tissues in response to stimuli, such as allergic responses, infections, or tumor growth [10][11][12][13][14][15][16][17][18][19]. Four chemokine receptors, CCR2, CCR5, CXCR3 and CX3CR1, have been shown to be particularly important for mouse NK-cell migration to various inflammatory stimulus [4,9]. However, other molecules such as CD62L, IFN-g, sphingosine 1-phosphate receptor, and TNF-a are also important for the NKcell migration in mice. For example, blocking CD62L with Ab prevents the egress of NK cells from blood into LN [4]. IFN-g modulates migration by inducing the production of CXCL10 (IP10) [20]. Thus, mice deficient in IFN-g also exhibit reduced CXCL10 production. In mice lacking sphingosine 1-phosphate receptor, NK cells accumulate in the LN and bone marrow while being absent from blood, spleen, or lungs [21]. Thus chemokine activation of NK cells is important for their recruitment to inflammatory sites. In both mice and humans, two main types of ''DC'' exist, conventional DC (cDC), including both lymphoid tissue-resident DC and migratory DC, and so-called plasmacytoid DC (pDC). In mice, cDC in the spleen can be further subdivided into the CD8a 1 and CD8a À populations. The former are involved in crosspr...

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Section: Resultssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Plasmacytoid dendritic cell‐induced migration and activation of NK cells in vivo

Persson

Chambers

2010

Eur J Immunol

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“…NK cells are known to enhance T cell priming by stimulating DC activation and secretion of IL-12 and IL-15, thus polarizing the response toward a Th1 phenotype (46,47). Activated DCs, in turn, can recruit NK cells to dLNs (48) and enhance their cytotoxic activity and IFN-g production (49). NK cell-derived IFN-g may also contribute to DC and macrophage activation and increase the susceptibility of tumor cells to CTL killing via upregulation of MHC class I expression (50).…”

Section: Discussionmentioning

confidence: 99%

Increased Numbers of Monocyte-Derived Dendritic Cells during Successful Tumor Immunotherapy with Immune-Activating Agents

Kühn

Hyde

Yang

et al. 2013

The Journal of Immunology

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Local treatment with selected TLR ligands or bacteria such as bacillus Calmette–Guérin increases antitumor immune responses and delays tumor growth. It is thought that these treatments may act by activating tumor-associated dendritic cells (DCs), thereby supporting the induction of antitumor immune responses. However, common parameters of successful immune activation have not been identified. We used mouse models to compare treatments with different immune-activating agents for the ability to delay tumor growth, improve priming of tumor-specific T cells, and induce early cytokine production and DC activation. Treatment with polyinosinic-polycytidylic acid or a combination of monosodium urate crystals and Mycobacterium smegmatis was effective at delaying the growth of s.c. B16 melanomas, orthotopic 4T1 mammary carcinomas, and reducing 4T1 lung metastases. In contrast, LPS, monosodium urate crystals, or M. smegmatis alone had no activity. Effective treatments required both NK1.1+ and CD8+ cells, and resulted in increased T cell priming and the infiltration of NK cells and CD8+ T cells in tumors. Unexpectedly, both effective and ineffective treatments increased DC numbers and the expression of costimulatory molecules in the tumor-draining lymph node. However, only effective treatments induced the rapid appearance of a population of monocyte-derived DCs in the draining lymph node, early release of IL-12p70 and IFN-γ, and low IL-10 in the serum. These results suggest that the activation of existing DC subsets is not sufficient for the induction of antitumor immune responses, whereas early induction of Th1 cytokines and monocyte-derived DCs are features of successful activation of antitumor immunity.

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Cytokine regulation of natural killer cell effector functions

2010

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Initially described as effectors of natural cytotoxicity and critical players for the control of viral infections and tumor growth, recent investigations unraveled more widespread functions for the natural killer (NK) cells. Through the establishment of a crosstalk with dendritic cells, NK cells promote T helper-1- and cytotoxic T lymphocyte-mediated immunity, whereas through the establishment of a crosstalk with macrophages, NK cells contribute to the activation of their microbicidal functions. Recent evidence has shown that NK cells also display memory, a characteristic thought to be privative of T and B cells, and that NK cells acquire their mature phenotype during a complex ontogeny program which tunes their activation threshold. Cytokines play critical roles in regulating all aspects of immune responses, including lymphoid development, homeostasis, differentiation, tolerance, and memory. Cytokines such as interleukin (IL)-2, IL-12, IL-15, IL-18, IL-21, and type I interferons constitute pivotal factors involved in the maturation, activation, and survival of NK cells. In addition, the discovery of novel cytokines is increasing the spectrum of soluble mediators that regulate NK cell immunobiology. In this review, we summarize and integrate novel concepts about the role of different cytokines in the regulation of NK cell function. We believe that a full understanding of how NK cells become activated and develop their effector functions in response to cytokines and other stimuli may lead to the development of novel immunotherapeutic strategies for the treatment of different types of cancer, viral infections, and chronic autoimmune diseases.

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IFN-γ-Dependent Recruitment of Mature CD27high NK Cells to Lymph Nodes Primed by Dendritic Cells

Cited by 60 publications

References 39 publications

Plasmacytoid dendritic cell‐induced migration and activation of NK cells in vivo

Plasmacytoid dendritic cell‐induced migration and activation of NK cells in vivo

Increased Numbers of Monocyte-Derived Dendritic Cells during Successful Tumor Immunotherapy with Immune-Activating Agents

Cytokine regulation of natural killer cell effector functions

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