scholarly journals Activation of Natural Killer Cells and Dendritic Cells upon Recognition of a Novel CD99-like Ligand by Paired Immunoglobulin-like Type 2 Receptor

2004 ◽  
Vol 199 (4) ◽  
pp. 525-533 ◽  
Author(s):  
Ikuo Shiratori ◽  
Kouetsu Ogasawara ◽  
Takashi Saito ◽  
Lewis L. Lanier ◽  
Hisashi Arase
Keyword(s):  
Innate Immunity ◽  
Dendritic Cells ◽  
Immune System ◽  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Regulatory Mechanism ◽  
Adaptor Protein ◽  
T Cell Lines

Paired receptors that consist of highly related activating and inhibitory receptors are widely involved in the regulation of the immune system. Here, we report a mouse orthologue of the human activating paired immunoglobulin-like type 2 receptor (PILR) β, which was cloned from a cDNA library of natural killer (NK) cells based on its ability to associate with the DAP12 signaling adaptor protein. The activating PILRβ was expressed not only on NK cells but also on dendritic cells and macrophages. Furthermore, we have identified a novel CD99-like molecule as a ligand for the activating PILRβ and inhibitory PILRα receptors. Transcripts of PILR ligand are present in many tissues, including some T cell lines. Cells expressing the PILR ligand specifically activated NK cells and dendritic cells that express the activating PILRβ. Our findings reveal a new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

scholarly journals Placentation and antitumor immunity regulated by a scaffolding protein in NK cells

2019 ◽  
Vol 4 (38) ◽  
pp. eaax9589
Author(s):  
Francesco Colucci
Keyword(s):  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Adaptor Protein ◽  
Scaffolding Protein ◽  
Trophoblast Invasion ◽  
Related Research ◽  
Research Article

Natural killer cells use the Gab3 adaptor protein to limit trophoblast invasion during pregnancy and to reject tumor cells. See the related Research Article by Sliz et al.

Production of interferons by dendritic cells, plasmacytoid cells, natural killer cells, and interferon-producing killer dendritic cells

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1165-1173 ◽  
Author(s):  
David Vremec ◽  
Meredith O'Keeffe ◽  
Hubertus Hochrein ◽  
Martina Fuchsberger ◽  
Irina Caminschi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Interferon Γ ◽  
Target Cells ◽  
Toll Like Receptor ◽  
Ifn Γ ◽  
Developmental Form ◽  
Early Developmental

Abstract The capacity of mouse spleen conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) to produce interferon-γ (IFN-γ) or IFN-α was assessed, and compared with that of natural killer (NK) cells and the recently identified interferon-producing killer dendritic cells (IKDCs), both of which are frequent contaminants in DC preparations. Fully developed cDCs or pDCs, if free of NK cells or IKDCs, showed little capacity for IFN-γ production. However, an early developmental form of the CD4−8+ cDC subtype, and the Ly6C− Ly49Q− pDC subtype, both were able to produce moderate amounts of IFN-γ, although less than IKDCs. In response to toll-like receptor 9 stimuli, both the Ly6C+ Ly49Q+ and the Ly6C− Ly49Q− pDC subtypes were effective producers of IFN-α. However, IKDCs, which efficiently produced IFN-γ and showed immediate cytotoxicity on NK target cells, did not produce IFN-α un-der these conditions.

scholarly journals A Chimeric IL-15/IL-15Rα Molecule Expressed on NFκB-Activated Dendritic Cells Supports Their Capability to Activate Natural Killer Cells

2021 ◽  
Vol 22 (19) ◽  
pp. 10227
Author(s):  
Naomi C. Bosch ◽  
Lena-Marie Martin ◽  
Caroline J. Voskens ◽  
Carola Berking ◽  
Barbara Seliger ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cellular Response ◽  
Nk Cell ◽  
Ex Vivo ◽  
Therapeutic Vaccine ◽  
Chimeric Protein ◽  
Hla Class I

Natural killer (NK) cells, members of the innate immune system, play an important role in the rejection of HLA class I negative tumor cells. Hence, a therapeutic vaccine, which can activate NK cells in addition to cells of the adaptive immune system might induce a more comprehensive cellular response, which could lead to increased tumor elimination. Dendritic cells (DCs) are capable of activating and expanding NK cells, especially when the NFκB pathway is activated in the DCs thereby leading to the secretion of the cytokine IL-12. Another prominent NK cell activator is IL-15, which can be bound by the IL-15 receptor alpha-chain (IL-15Rα) to be transpresented to the NK cells. However, monocyte-derived DCs do neither secrete IL-15, nor express the IL-15Rα. Hence, we designed a chimeric protein consisting of IL-15 and the IL-15Rα. Upon mRNA electroporation, the fusion protein was detectable on the surface of the DCs, and increased the potential of NFκB-activated, IL-12-producing DC to activate NK cells in an autologous cell culture system with ex vivo-generated cells from healthy donors. These data show that a chimeric IL-15/IL-15Rα molecule can be expressed by monocyte-derived DCs, is trafficked to the cell surface, and is functional regarding the activation of NK cells. These data represent an initial proof-of-concept for an additional possibility of further improving cellular DC-based immunotherapies of cancer.

scholarly journals Functions of Dendritic Cells and Its Association with Intestinal Diseases

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 583
Author(s):  
Ze-Jun Yang ◽  
Bo-Ya Wang ◽  
Tian-Tian Wang ◽  
Fei-Fei Wang ◽  
Yue-Xin Guo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Immune System ◽  
Regulatory Mechanism ◽  
Intestinal Tumors ◽  
Regulatory Relationship ◽  
Intestinal Diseases ◽  
Inflammatory Bowel ◽  
Plasmacytoid Dcs

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.

scholarly journals Natural Killer Cell Mobilization in Breast and Prostate Cancer Survivors: The Implications of Altered Stress Hormones Following Acute Exercise

Endocrines ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 121-132
Author(s):  
Erik D. Hanson ◽  
Lauren C. Bates ◽  
Kaileigh Moertl ◽  
Elizabeth S. Evans
Keyword(s):  
Prostate Cancer ◽  
Immune System ◽  
Cancer Survivors ◽  
Nk Cells ◽  
Natural Killer ◽  
Acute Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Current Evidence ◽  
Cell Mobilization

Natural killer (NK) cells from the innate immune system are integral to overall immunity and also in managing the tumor burden during cancer. Breast (BCa) and prostate cancer (PCa) are the most common tumors in U.S. adults. Both BCa and PCa are frequently treated with hormone suppression therapies that are associated with numerous adverse effects including direct effects on the immune system. Regular exercise is recommended for cancer survivors to reduce side effects and improve quality of life. Acute exercise is a potent stimulus for NK cells in healthy individuals with current evidence indicating that NK mobilization in individuals with BCa and PCa is comparable. NK cell mobilization results from elevations in shear stress and catecholamine levels. Despite a normal NK cell response to exercise, increases in epinephrine are attenuated in BCa and PCa. The significance of this potential discrepancy still needs to be determined. However, alterations in adrenal hormone signaling are hypothesized to be due to chronic stress during cancer treatment. Additional compensatory factors induced by exercise are reviewed along with recommendations on standardized approaches to be used in exercise immunology studies involving oncology populations.

scholarly journals Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shoeib Moradi ◽  
Sanda Stankovic ◽  
Geraldine M. O’Connor ◽  
Phillip Pymm ◽  
Bruce J. MacLachlan ◽  
...  
Keyword(s):  
Natural Killer Cells ◽  
Human Leukocyte Antigen ◽  
Nk Cells ◽  
Natural Killer ◽  
Crystal Structures ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Functional Differences ◽  
Molecular Bases

AbstractThe closely related inhibitory killer-cell immunoglobulin-like receptors (KIR), KIR2DL2 and KIR2DL3, regulate the activation of natural killer cells (NK) by interacting with the human leukocyte antigen-C1 (HLA-C1) group of molecules. KIR2DL2, KIR2DL3 and HLA-C1 are highly polymorphic, with this variation being associated with differences in the onset and progression of some human diseases. However, the molecular bases underlying these associations remain unresolved. Here, we determined the crystal structures of KIR2DL2 and KIR2DL3 in complex with HLA-C*07:02 presenting a self-epitope. KIR2DL2 differed from KIR2DL3 in docking modality over HLA-C*07:02 that correlates with variabilty of recognition of HLA-C1 allotypes. Mutagenesis assays indicated differences in the mechanism of HLA-C1 allotype recognition by KIR2DL2 and KIR2DL3. Similarly, HLA-C1 allotypes differed markedly in their capacity to inhibit activation of primary NK cells. These functional differences derive, in part, from KIR2DS2 suggesting KIR2DL2 and KIR2DL3 binding geometries combine with other factors to distinguish HLA-C1 functional recognition.

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