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  1. AU="Aldridge, Daniel L"
  2. AU=Gross Lissy Z F AU=Gross Lissy Z F
  3. AU="DeVita, Robert"
  4. AU=Berkenstock Meghan K
  5. AU=Saleh Mohammed
  6. AU="Ganesan, Anuradha"
  7. AU="Ye, Yi-Fan"
  8. AU="Astasov-Frauenhoffer, Monika"
  9. AU="Ferrer-Diaz, Alejandra I"
  10. AU="Iwata, Miko"

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  1. Artikel ; Online: Endogenous IL-27 during toxoplasmosis limits early monocyte responses and their inflammatory activation by pathological T cells.

    Aldridge, Daniel L / Moodley, Devapregasan / Park, Jeongho / Phan, Anthony T / Rausch, Matthew / White, Kerry F / Ren, Yue / Golin, Karin / Radaelli, Enrico / Kedl, Ross / Holland, Pamela M / Hill, Jonathan / Hunter, Christopher A

    mBio

    2024  Band 15, Heft 3, Seite(n) e0008324

    Abstract: Mice that lack the genes for IL-27, or the IL-27 receptor, and infected with : Importance: The molecule IL-27 is critical in limiting the immune response to the ... ...

    Abstract Mice that lack the genes for IL-27, or the IL-27 receptor, and infected with
    Importance: The molecule IL-27 is critical in limiting the immune response to the parasite
    Mesh-Begriff(e) Animals ; Mice ; Interleukin-27/metabolism ; Mice, Inbred C57BL ; Monocytes ; T-Lymphocytes ; Toxoplasma ; Toxoplasmosis/parasitology
    Chemische Substanzen Interleukin-27 ; Il27 protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2024-02-20
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00083-24
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Limited Impact of the Inhibitory Receptor TIGIT on NK and T Cell Responses during

    Aldridge, Daniel L / Phan, Anthony T / de Waal Malefyt, Rene / Hunter, Christopher A

    ImmunoHorizons

    2021  Band 5, Heft 6, Seite(n) 384–394

    Abstract: Resistance to the ... ...

    Abstract Resistance to the parasite
    Mesh-Begriff(e) Animals ; Antigens, Differentiation, T-Lymphocyte/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Disease Models, Animal ; Female ; Humans ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Male ; Mice ; Mice, Knockout ; Parasite Load ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Receptors, Virus/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Toxoplasma/immunology ; Toxoplasma/isolation & purification ; Toxoplasmosis/blood ; Toxoplasmosis/immunology ; Toxoplasmosis/parasitology
    Chemische Substanzen Antigens, Differentiation, T-Lymphocyte ; CD226 antigen ; Receptors, Immunologic ; Receptors, Virus ; T cell Ig and ITIM domain protein, mouse ; poliovirus receptor
    Sprache Englisch
    Erscheinungsdatum 2021-06-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2573-7732
    ISSN (online) 2573-7732
    DOI 10.4049/immunohorizons.2100007
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Harmine enhances the activity of the HIV-1 latency-reversing agents ingenol A and SAHA.

    Taylor, Jared P / Armitage, Lucas H / Aldridge, Daniel L / Cash, Melanie N / Wallet, Mark A

    Biology open

    2020  Band 9, Heft 12

    Abstract: Infection with human immunodeficiency virus 1 (HIV-1) remains incurable because long-lived, latently-infected cells persist during prolonged antiretroviral therapy. Attempts to pharmacologically reactivate and purge the latent reservoir with latency ... ...

    Abstract Infection with human immunodeficiency virus 1 (HIV-1) remains incurable because long-lived, latently-infected cells persist during prolonged antiretroviral therapy. Attempts to pharmacologically reactivate and purge the latent reservoir with latency reactivating agents (LRAs) such as protein kinase C (PKC) agonists (e.g. ingenol A) or histone deacetylase (HDAC) inhibitors (e.g. SAHA) have shown promising but incomplete efficacy. Using the J-Lat T cell model of HIV latency, we found that the plant-derived compound harmine enhanced the efficacy of existing PKC agonist LRAs in reactivating latently-infected cells. Treatment with harmine increased not only the number of reactivated cells but also increased HIV transcription and protein expression on a per-cell basis. Importantly, we observed a synergistic effect when harmine was used in combination with ingenol A and the HDAC inhibitor SAHA. An investigation into the mechanism revealed that harmine, when used with LRAs, increased the activity of NFκB, MAPK p38, and ERK1/2. Harmine treatment also resulted in reduced expression of HEXIM1, a negative regulator of transcriptional elongation. Thus, harmine enhanced the effects of LRAs by increasing the availability of transcription factors needed for HIV reactivation and promoting transcriptional elongation. Combination therapies with harmine and LRAs could benefit patients by achieving deeper reactivation of the latent pool of HIV provirus.
    Mesh-Begriff(e) CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; Diterpenes/pharmacology ; Gene Expression Regulation/drug effects ; HIV Infections/immunology ; HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/physiology ; Harmine/pharmacology ; Humans ; Lymphocyte Activation/drug effects ; Nylons/pharmacology ; Protein Kinase C/metabolism ; Pyrroles/pharmacology ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Virus Activation/drug effects ; Virus Latency/drug effects
    Chemische Substanzen Diterpenes ; HEXIM1 protein, human ; Nylons ; Pyrroles ; RNA-Binding Proteins ; SAHA-PIP-delta ; Transcription Factors ; Harmine (4FHH5G48T7) ; Protein Kinase C (EC 2.7.11.13) ; ingenol (IC77UZI9G8)
    Sprache Englisch
    Erscheinungsdatum 2020-12-21
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2632264-X
    ISSN 2046-6390 ; 2046-6390
    ISSN (online) 2046-6390
    ISSN 2046-6390
    DOI 10.1242/bio.052969
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii.

    Clark, Joseph T / Weizman, Orr-El / Aldridge, Daniel L / Shallberg, Lindsey A / Eberhard, Julia / Lanzar, Zachary / Wasche, Devon / Huck, John D / Zhou, Ting / Ring, Aaron M / Hunter, Christopher A

    Cell reports

    2023  Band 42, Heft 3, Seite(n) 112147

    Abstract: Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of interferon (IFN)-γ, a key factor in resistance to Toxoplasma gondii, but previous work has shown a limited role for endogenous IL-18 in control of this parasite. Although ... ...

    Abstract Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of interferon (IFN)-γ, a key factor in resistance to Toxoplasma gondii, but previous work has shown a limited role for endogenous IL-18 in control of this parasite. Although infection with T. gondii results in release of IL-18, the production of IFN-γ induces high levels of the IL-18 binding protein (IL-18BP). Antagonism of IL-18BP with a "decoy-to-the-decoy" (D2D) IL-18 construct that does not signal but rather binds IL-18BP results in enhanced innate lymphoid cell (ILC) and T cell responses and improved parasite control. In addition, the use of IL-18 resistant to IL-18BP ("decoy-resistant" IL-18 [DR-18]) is more effective than exogenous IL-18 at promoting innate resistance to infection. DR-18 enhances CD4
    Mesh-Begriff(e) Humans ; Animals ; Toxoplasma ; Interleukin-18/metabolism ; Killer Cells, Natural ; Interleukin-12/metabolism ; Immunity, Innate ; Toxoplasmosis, Animal
    Chemische Substanzen Interleukin-18 ; interleukin-18 binding protein ; Interleukin-12 (187348-17-0)
    Sprache Englisch
    Erscheinungsdatum 2023-02-23
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112147
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Single-cell analysis highlights differences in druggable pathways underlying adaptive or fibrotic kidney regeneration.

    Balzer, Michael S / Doke, Tomohito / Yang, Ya-Wen / Aldridge, Daniel L / Hu, Hailong / Mai, Hung / Mukhi, Dhanunjay / Ma, Ziyuan / Shrestha, Rojesh / Palmer, Matthew B / Hunter, Christopher A / Susztak, Katalin

    Nature communications

    2022  Band 13, Heft 1, Seite(n) 4018

    Abstract: The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic repair are poorly understood. We developed a model of adaptive and fibrotic kidney regeneration by titrating ischemic injury dose. We ... ...

    Abstract The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic repair are poorly understood. We developed a model of adaptive and fibrotic kidney regeneration by titrating ischemic injury dose. We performed detailed biochemical and histological analysis and profiled transcriptomic changes at bulk and single-cell level (> 110,000 cells) over time. Our analysis highlights kidney proximal tubule cells as key susceptible cells to injury. Adaptive proximal tubule repair correlated with fatty acid oxidation and oxidative phosphorylation. We identify a specific maladaptive/profibrotic proximal tubule cluster after long ischemia, which expresses proinflammatory and profibrotic cytokines and myeloid cell chemotactic factors. Druggability analysis highlights pyroptosis/ferroptosis as vulnerable pathways in these profibrotic cells. Pharmacological targeting of pyroptosis/ferroptosis in vivo pushed cells towards adaptive repair and ameliorates fibrosis. In summary, our single-cell analysis defines key differences in adaptive and fibrotic repair and identifies druggable pathways for pharmacological intervention to prevent kidney fibrosis.
    Mesh-Begriff(e) Acute Kidney Injury/drug therapy ; Acute Kidney Injury/genetics ; Acute Kidney Injury/metabolism ; Fibrosis ; Humans ; Kidney/metabolism ; Regeneration ; Single-Cell Analysis
    Sprache Englisch
    Erscheinungsdatum 2022-07-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-31772-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: B cells promote CD8 T cell primary and memory responses to subunit vaccines.

    Klarquist, Jared / Cross, Eric W / Thompson, Scott B / Willett, Benjamin / Aldridge, Daniel L / Caffrey-Carr, Alayna K / Xu, Zhenming / Hunter, Christopher A / Getahun, Andrew / Kedl, Ross M

    Cell reports

    2021  Band 36, Heft 8, Seite(n) 109591

    Abstract: The relationship between B cells and CD4 T cells has been carefully studied, revealing a collaborative effort in which B cells promote the activation, differentiation, and expansion of CD4 T cells while the so-called "helper" cells provide signals to B ... ...

    Abstract The relationship between B cells and CD4 T cells has been carefully studied, revealing a collaborative effort in which B cells promote the activation, differentiation, and expansion of CD4 T cells while the so-called "helper" cells provide signals to B cells, influencing their class switching and fate. Interactions between B cells and CD8 T cells are not as well studied, although CD8 T cells exhibit an accelerated contraction after certain infections in B-cell-deficient mice. Here, we find that B cells significantly enhance primary CD8 T cell responses after vaccination. Moreover, memory CD8 numbers and function are impaired in B-cell-deficient animals, leading to increased susceptibility to bacterial challenge. We also show that interleukin-27 production by B cells contributes to their impact on primary, but not memory, CD8 responses. Better understanding of the interactions between CD8 T cells and B cells may aid in the design of more effective future vaccine strategies.
    Mesh-Begriff(e) Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; COVID-19/immunology ; Humans ; Immunologic Memory ; Interleukin-27/immunology ; Interleukin-27/metabolism ; Lymphocyte Count ; Mice ; Mice, Inbred C57BL ; Receptors, Virus/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; Vaccination ; Vaccines, Subunit/immunology
    Chemische Substanzen Interleukin-27 ; Receptors, Virus ; Spike Glycoprotein, Coronavirus ; Vaccines, Subunit ; spike protein, SARS-CoV-2
    Sprache Englisch
    Erscheinungsdatum 2021-08-25
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109591
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis.

    Doke, Tomohito / Abedini, Amin / Aldridge, Daniel L / Yang, Ya-Wen / Park, Jihwan / Hernandez, Christina M / Balzer, Michael S / Shrestra, Rojesh / Coppock, Gaia / Rico, Juan M Inclan / Han, Seung Yub / Kim, Junhyong / Xin, Sheng / Piliponsky, Adrian M / Angelozzi, Marco / Lefebvre, Veronique / Siracusa, Mark C / Hunter, Christopher A / Susztak, Katalin

    Nature immunology

    2022  Band 23, Heft 6, Seite(n) 947–959

    Abstract: Inflammation is an important component of fibrosis but immune processes that orchestrate kidney fibrosis are not well understood. Here we apply single-cell sequencing to a mouse model of kidney fibrosis. We identify a subset of kidney tubule cells with a ...

    Abstract Inflammation is an important component of fibrosis but immune processes that orchestrate kidney fibrosis are not well understood. Here we apply single-cell sequencing to a mouse model of kidney fibrosis. We identify a subset of kidney tubule cells with a profibrotic-inflammatory phenotype characterized by the expression of cytokines and chemokines associated with immune cell recruitment. Receptor-ligand interaction analysis and experimental validation indicate that CXCL1 secreted by profibrotic tubules recruits CXCR2
    Mesh-Begriff(e) Animals ; Basophils ; Fibrosis ; Humans ; Kidney/metabolism ; Kidney Tubules ; Mice ; Renal Insufficiency, Chronic/metabolism ; Single-Cell Analysis
    Sprache Englisch
    Erscheinungsdatum 2022-05-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01200-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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