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  1. Article ; Online: Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from Olea europaea Pollen.

    Abos Gracia, Beatriz / López Relaño, Juan / Revilla, Ana / Castro, Lourdes / Villalba, Mayte / Martín Adrados, Beatriz / Regueiro, Jose Ramon / Fernández-Malavé, Edgar / Martínez Naves, Eduardo / Gómez Del Moral, Manuel

    International archives of allergy and immunology

    2017  Volume 173, Issue 1, Page(s) 12–22

    Abstract: Background: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids ...

    Abstract Background: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study was to analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs).
    Methods: Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA.
    Results: Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ.
    Conclusions: Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses.
    MeSH term(s) Allergens/immunology ; Antigen-Presenting Cells/immunology ; Antigens, CD1d/immunology ; Cytokines/immunology ; Humans ; Lipids/immunology ; Natural Killer T-Cells/immunology ; Olea/immunology ; Pollen/immunology
    Chemical Substances Allergens ; Antigens, CD1d ; CD1D protein, human ; Cytokines ; Lipids
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1108932-5
    ISSN 1423-0097 ; 1018-2438
    ISSN (online) 1423-0097
    ISSN 1018-2438
    DOI 10.1159/000467394
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Human Invariant Natural Killer T Cells Respond to Antigen-Presenting Cells Exposed to Lipids from ; Pollen

    Abos Gracia, Beatriz / López Relaño, Juan / Revilla, Ana / Castro, Lourdes / Villalba, Mayte / Martín Adrados, Beatriz / Regueiro, Jose Ramon / Fernández-Malavé, Edgar / Martínez Naves, Eduardo / Gómez del Moral, Manuel

    International Archives of Allergy and Immunology

    2017  Volume 173, Issue 1, Page(s) 12–22

    Abstract: Background: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study wasto analyze the effect of olive pollen lipids ... ...

    Institution Departments of Immunology and Cell Biology, Faculty of Medicine, and 12 de Octubre Health Research Institute (imas12), and Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Complutense University, Madrid, Spain
    Abstract Background: Allergic sensitization might be influenced by the lipids present in allergens, which can be recognized by natural killer T (NKT) cells on antigen-presenting cells (APCs). The aim of this study wasto analyze the effect of olive pollen lipids in human APCs, including monocytes as well as monocyte-derived macrophages (Mϕ) and dendritic cells (DCs). Methods: Lipids were extracted from olive (Olea europaea) pollen grains. Invariant (i)NKT cells, monocytes, Mϕ, and DCs were obtained from buffy coats of healthy blood donors, and their cell phenotype was determined by flow cytometry. iNKT cytotoxicity was measured using a lactate dehydrogenase assay. Gene expression of CD1A and CD1D was performed by RT-PCR, and the production of IL-6, IL-10, IL-12, and TNF-α cytokines by monocytes, Mϕ, and DCs was measured by ELISA. Results: Our results showed that monocytes and monocyte-derived Mϕ treated with olive pollen lipids strongly activate iNKT cells. We observed several phenotypic modifications in the APCs upon exposure to pollen-derived lipids. Both Mϕ and monocytes treated with olive pollen lipids showed an increase in CD1D gene expression, whereas upregulation of cell surface CD1d protein occurred only in Mϕ. Furthermore, DCs differentiated in the presence of human serum enhance their surface CD1d expression when exposed to olive pollen lipids. Finally, olive pollen lipids were able to stimulate the production of IL-6 but downregulated the production of lipopolysaccharide- induced IL-10 by Mϕ. Conclusions: Olive pollen lipids alter the phenotype of monocytes, Mϕ, and DCs, resulting in the activation of NKT cells, which have the potential to influence allergic immune responses.
    Keywords CD1d ; Invariant natural killer T cells ; Pollen lipids
    Language English
    Publishing date 2017-05-10
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Molecules and Cells in Allergy - Original Paper
    ZDB-ID 1108932-5
    ISSN 1423-0097 ; 1018-2438
    ISSN (online) 1423-0097
    ISSN 1018-2438
    DOI 10.1159/000467394
    Database Karger publisher's database

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  3. Article ; Online: A novel MEK-ERK-AMPK signaling axis controls chemokine receptor CCR7-dependent survival in human mature dendritic cells.

    López-Cotarelo, Pilar / Escribano-Díaz, Cristina / González-Bethencourt, Ivan Luis / Gómez-Moreira, Carolina / Deguiz, María Laura / Torres-Bacete, Jesús / Gómez-Cabañas, Laura / Fernández-Barrera, Jaime / Delgado-Martín, Cristina / Mellado, Mario / Regueiro, José Ramón / Miranda-Carús, María Eugenia / Rodríguez-Fernández, José Luis

    The Journal of biological chemistry

    2014  Volume 290, Issue 2, Page(s) 827–840

    Abstract: Chemokine receptor CCR7 directs mature dendritic cells (mDCs) to secondary lymph nodes where these cells regulate the activation of T cells. CCR7 also promotes survival in mDCs, which is believed to take place largely through Akt-dependent signaling ... ...

    Abstract Chemokine receptor CCR7 directs mature dendritic cells (mDCs) to secondary lymph nodes where these cells regulate the activation of T cells. CCR7 also promotes survival in mDCs, which is believed to take place largely through Akt-dependent signaling mechanisms. We have analyzed the involvement of the AMP-dependent kinase (AMPK) in the control of CCR7-dependent survival. A pro-apoptotic role for AMPK is suggested by the finding that pharmacological activators induce apoptosis, whereas knocking down of AMPK with siRNA extends mDC survival. Pharmacological activation of AMPK also induces apoptosis of mDCs in the lymph nodes. Stimulation of CCR7 leads to inhibition of AMPK, through phosphorylation of Ser-485, which was mediated by G(i)/Gβγ, but not by Akt or S6K, two kinases that control the phosphorylation of AMPK on Ser-485 in other settings. Using selective pharmacological inhibitors, we show that CCR7-induced phosphorylation of AMPK on Ser-485 is mediated by MEK and ERK. Coimmunoprecipitation analysis and proximity ligation assays indicate that AMPK associates with ERK, but not with MEK. These results suggest that in addition to Akt-dependent signaling mechanisms, CCR7 can also promote survival of mDCs through a novel MEK1/2-ERK1/2-AMPK signaling axis. The data also suggest that AMPK may be a potential target to modulate mDC lifespan and the immune response.
    MeSH term(s) AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Apoptosis/genetics ; Cell Survival ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Humans ; Immunity, Innate/genetics ; MAP Kinase Kinase 1/genetics ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Kinase 2/genetics ; MAP Kinase Kinase 2/metabolism ; Mitogen-Activated Protein Kinase 3/genetics ; Phosphorylation ; Receptors, CCR7/genetics ; Receptors, CCR7/metabolism ; Signal Transduction/genetics ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
    Chemical Substances CCR7 protein, human ; Receptors, CCR7 ; MAP2K2 protein, human (EC 2.7.1.-) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) ; AMP-Activated Protein Kinases (EC 2.7.11.31) ; MAP Kinase Kinase 1 (EC 2.7.12.2) ; MAP Kinase Kinase 2 (EC 2.7.12.2) ; MAP2K1 protein, human (EC 2.7.12.2)
    Language English
    Publishing date 2014-11-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M114.596551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Gain-of-function mutation in PIK3R1 in a patient with a narrow clinical phenotype of respiratory infections.

    Martínez-Saavedra, María Teresa / García-Gomez, Sonia / Domínguez Acosta, Ana / Mendoza Quintana, Juan Jesús / Páez, Jesús Poch / García-Reino, Eduardo J / Camps, Gracián / Martinez-Barricarte, Rubén / Itan, Yuval / Boisson, Bertrand / Sánchez-Ramón, Silvia / Regueiro, José Ramón / Casanova, Jean-Laurent / Rodríguez-Gallego, Carlos / Pérez de Diego, Rebeca

    Clinical immunology (Orlando, Fla.)

    2016  Volume 173, Page(s) 117–120

    Abstract: Antibody deficiencies can be caused by a variety of defects that interfere with B-cell development, maturation, and/or function. Using whole-exome sequencing we found a PIK3R1 mutation in a patient with hypogammaglobulinemia and a narrow clinical ... ...

    Abstract Antibody deficiencies can be caused by a variety of defects that interfere with B-cell development, maturation, and/or function. Using whole-exome sequencing we found a PIK3R1 mutation in a patient with hypogammaglobulinemia and a narrow clinical phenotype of respiratory infections. Early diagnosis is crucial; careful analysis of B and T-cells followed by genetic analyses may help to distinguish activated PI3K-delta syndrome (APDS) from other, less severe, predominantly antibody deficiencies.
    MeSH term(s) Agammaglobulinemia/genetics ; Agammaglobulinemia/immunology ; B-Lymphocytes/immunology ; Child ; Female ; Humans ; Mutation ; Phenotype ; Phosphatidylinositol 3-Kinases/genetics ; Respiratory Tract Infections/genetics ; Respiratory Tract Infections/immunology ; T-Lymphocytes/immunology
    Chemical Substances PIK3R1 protein, human (EC 2.7.1.-) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-)
    Language English
    Publishing date 2016-12
    Publishing country United States
    Document type Case Reports ; Letter
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2016.09.011
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  5. Article ; Online: New human combined immunodeficiency caused by interferon regulatory factor 4 (IRF4) deficiency inherited by uniparental isodisomy.

    Bravo García-Morato, María / Aracil Santos, Francisco Javier / Briones, Alejandro Contreras / Blázquez Moreno, Alfonso / Del Pozo Maté, Ángela / Domínguez-Soto, Ángeles / Beato Merino, María José / Del Pino Molina, Lucía / Torres Canizales, Juan / Marin, Ana Victoria / Vallespín García, Elena / Feito Rodríguez, Marta / Plaza López Sabando, Diego / Jiménez-Reinoso, Anaïs / Mozo Del Castillo, Yasmina / Sanz Santaeufemia, Francisco José / de Lucas-Laguna, Raúl / Cárdenas, Paula P / Casamayor Polo, Laura /
    Coronel Díaz, María / Valés-Gómez, Mar / Roldán Santiago, Ernesto / Ferreira Cerdán, Antonio / Nevado Blanco, Julián / Corbí, Ángel L / Reyburn, Hugh T / Regueiro, José Ramón / López-Granados, Eduardo / Rodríguez Pena, Rebeca

    The Journal of allergy and clinical immunology

    2018  Volume 141, Issue 5, Page(s) 1924–1927.e18

    MeSH term(s) Animals ; Cells, Cultured ; Female ; Humans ; Immunologic Deficiency Syndromes/immunology ; Infant ; Interferon Regulatory Factors/immunology ; Mice ; Uniparental Disomy/immunology
    Chemical Substances Interferon Regulatory Factors ; interferon regulatory factor-4
    Language English
    Publishing date 2018-03-02
    Publishing country United States
    Document type Case Reports ; Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2017.12.995
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