Human Decidual Natural Killer Cells Express the Receptor for and Respond to the Cytokine Interleukin 151

Verma, Sanjay; Hiby, Susan E.; Loke, Y.W.; King, Ashley

doi:10.1095/biolreprod62.4.959

Cited by 261 publications

(187 citation statements)

References 56 publications

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“…Similarly, IFN-γ induces IL-15 mRNA expression in monocytes and NK cells [49,50,51]. The concentrations of IL-15 produced by human islets were low, similar to data obtained in other cell types [49,52]. It has been shown that picomolar amounts of IL-15 are effective in maintaining NK cell survival in serum-free media [49], suggesting that the observed IL-15 production by human islets might be physiologically relevant.…”

Section: Discussionsupporting

confidence: 54%

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

et al. 2003

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Aims/hypothesis. Cytokines and chemokines are important mediators of immune responses due to their ability to recruit and activate leukocytes. Using microarray analysis we observed that rat beta cells exposed to IL-1β and IFN-γ have increased mRNA levels of chemokines and IL-15. The aim of this study was to characterize the expression of IP-10, MIP-3α, fractalkine and IL-15 in rat beta cells, human pancreatic islets, and in islets isolated from NOD mice, both during the pre-diabetic period and following islet transplantation. Methods. FACS-purified rat beta cells and human islets were cultured with IL-1β, IFN-γ and/or TNF-α. Islets were isolated from NOD or BALB/c mice at different ages. For syngeneic islet transplantation, 2-or 3-week-old NOD islets were grafted under the kidney capsule of spontaneously diabetic NOD recipients. Chemokine and IL-15 mRNA expression and protein release were evaluated, respectively, by RT-PCR and ELISA.Results. Human islets and rat beta cells express IP-10, MIP-3α, fractalkine and IL-15 mRNAs upon exposure to cytokines. The expression of IL-15, IP-10 and fractalkine is regulated by IFN-γ, while the expression of MIP-3α is IL-1β-dependent. Moreover, cytokines induced IL-15, IP-10, Mig, I-TAC and MIP-3α protein accumulation in culture medium from human islets. In vivo, there was an age-related increase in IL-15, IP-10 and MIP-3α expression in islets isolated from NOD mice. Following syngeneic islet transplantation, increased expression of IL-1β, IFN-γ, fractalkine, IP-10, MCP-1 and MIP-3α mRNAs were observed in the grafts. Conclusion/interpretation. Cytokine-exposed islets or beta cells express chemokines and IL-15. This could contribute to the recruitment and activation of mononuclear cells and development of insulitis in early Type 1 diabetes and during graft destruction. [Diabetologia (2003) 46:255-266] Keywords Type 1 diabetes mellitus, chemokines, IL-15, NOD mice, beta cells, interferon-γ, interleukin-1β, pancreatic islets, islet transplantation, insulitis.

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Section: Discussionsupporting

confidence: 54%

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

et al. 2003

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“…31 It is reasonable to hypothesize that the unique functional properties of dNK cells might be attributed to the particular cytokine milieu in the decidua. 32 In this study, we demonstrated that CD3 2 CD56 bright CD25 1 dNK cells preferentially localize to the maternal/fetal interface in early human pregnancy, and we also found that this cell subset displays a more activated phenotype than CD3 2 CD56 bright CD25 2 dNK cells. Furthermore, coculture of pNK with trophoblasts increased CD25 expression and the frequency of TGF-b-and IL-8-producing pNK cells.…”

Section: Discussionsupporting

confidence: 63%

CD56brightCD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

Piao

et al. 2014

Cell Mol Immunol

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Decidual natural killer (dNK) cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3 2 CD56 bright CD25 1 phenotype. We found that CD56 bright CD25 1 NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25 1 dNK cells account for approximately 75% of CD25-expressing decidual immune cells (DICs). However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25 1 NK cells. Furthermore, CD25 1 and CD25 2 dNK cells exhibit distinct phenotypes: CD25 1 dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK (pNK) cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25 1 dNK cells and contributes to the accumulation of CD3 2 CD56 bright CD25 1 dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3 2 CD56 bright CD25 1 dNK cells, which exert a regulating effect at the maternal/fetal interface.

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“…Published data obtained from in situ hybridization studies suggest that macrophages present in the pregnant mouse uterus may be responsible for the production of IL-15 [22], and it has also been shown that macrophages are the major source of IL-12 and IL-18 in most tissues [23,24]. These cytokines were recently shown to be capable of activating NK cells [25,26], and King and co-workers described IL-15 receptor expression on human decidual NK cells [27]. Impaired remodeling of maternal vessels, a hypocellular decidua and decreased development of the metrial gland observed in implantation sites with inhibited recruitment of a4b7 + leukocytes suggest altered uNK cell function, although litter size and birth weight in both b7-integrin -/-and P-selectin -/-mice are comparable to those of untreated or Hermes-1-treated wild-type pregnancies as also reported by Croy et al [20].…”

Section: Discussionmentioning

confidence: 98%

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

et al. 2004

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Leukocyte recruitment to the pregnant mouse uterus has been suggested to be associated with highly regulated expression of distinct patterns of vascular adhesion receptors. One of the most striking observations is the combined expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and P-selectin by maternal vessels of the vascular zone during the critical period of initial placenta development. The predominant cell population within these vessels is of the monocyte/macrophage lineage and expresses the mucosal integrin a4b7, which represents the ligand for MAdCAM-1; neutrophils and lymphocytes are rare. To directly assess the importance of identified adhesion receptors, we undertook longterm in vivo inhibition studies using monoclonal antibodies to inhibit the contribution of MAdCAM-1 in leukocyte trafficking to the decidua or to deplete a4b7 + leukocytes. In addition, implantation sites of mouse strains genetically deficient in specific adhesion receptors were investigated. Our results underline the importance of predicted adhesion pathways in the recruitment of monocyte-like cells, especially those expressing a4b7. Interestingly, maternal/ fetal units with inhibited recruitment of a4b7 + leukocytes or the absence of these cells are characterized by reduced size and frequency of uterine NK cells.

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Human Decidual Natural Killer Cells Express the Receptor for and Respond to the Cytokine Interleukin 151

Cited by 261 publications

References 56 publications

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

CD56brightCD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

Functional involvement of P‐selectin and MAdCAM‐1 in the recruitment of α4β7‐integrin‐expressing monocyte‐like cells to the pregnant mouse uterus

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