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  1. Article ; Online: Aire in Autoimmunity.

    Miller, Corey N / Waterfield, Michael R / Gardner, James M / Anderson, Mark S

    Annual review of immunology

    2024  

    Abstract: The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced ... ...

    Abstract The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis. Expected final online publication date for the
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 604953-9
    ISSN 1545-3278 ; 0732-0582
    ISSN (online) 1545-3278
    ISSN 0732-0582
    DOI 10.1146/annurev-immunol-090222-101050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: ATF7ip Targets Transposable Elements for H3K9me3 Deposition to Modify CD8

    Sin, Jun Hyung / Kashyap, Sujit / Acenas, Dante / Cortez, Jessica T / Lee, James / Marson, Alexander / Matloubian, Mehrdad / Waterfield, Michael R

    Journal of immunology (Baltimore, Md. : 1950)

    2022  Volume 208, Issue 5, Page(s) 1155–1169

    Abstract: ... ...

    Abstract CD8
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Chromatin Immunoprecipitation ; DNA Transposable Elements/genetics ; Gene Deletion ; Gene Silencing ; Histones/genetics ; Humans ; Immunologic Memory/immunology ; Interleukin-2/biosynthesis ; Interleukin-2/metabolism ; Listeria monocytogenes/immunology ; Listeriosis/immunology ; Listeriosis/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Interleukin-7/biosynthesis ; Receptors, Interleukin-7/genetics ; Receptors, Interleukin-7/metabolism ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
    Chemical Substances Atf7ip protein, mouse ; DNA Transposable Elements ; Histones ; Interleukin-2 ; Receptors, Interleukin-7 ; Repressor Proteins
    Language English
    Publishing date 2022-02-02
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2100996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ikaros is a principal regulator of Aire

    Sin, Jun Hyung / Sucharov, Juliana / Kashyap, Sujit / Wang, Yi / Proekt, Irina / Liu, Xian / Parent, Audrey V / Gupta, Alexander / Kastner, Philippe / Chan, Susan / Gardner, James M / Ntranos, Vasilis / Miller, Corey N / Anderson, Mark S / Schjerven, Hilde / Waterfield, Michael R

    Science immunology

    2023  Volume 8, Issue 88, Page(s) eabq3109

    Abstract: Mutations in the gene encoding the zinc-finger transcription factor Ikaros ( ...

    Abstract Mutations in the gene encoding the zinc-finger transcription factor Ikaros (
    MeSH term(s) Humans ; Mice ; Animals ; Central Tolerance ; Cell Differentiation ; Thymus Gland ; Transcription Factors ; Gene Expression Regulation
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2023-10-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abq3109
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  4. Article ; Online: The epigenetic regulator ATF7ip inhibits

    Sin, Jun Hyung / Zuckerman, Cassandra / Cortez, Jessica T / Eckalbar, Walter L / Erle, David J / Anderson, Mark S / Waterfield, Michael R

    The Journal of experimental medicine

    2019  Volume 216, Issue 9, Page(s) 2024–2037

    Abstract: T helper 17 cells (Th17) are critical for fighting infections at mucosal surfaces; however, they have also been found to contribute to the pathogenesis of multiple autoimmune diseases and have been targeted therapeutically. Due to the role of Th17 cells ... ...

    Abstract T helper 17 cells (Th17) are critical for fighting infections at mucosal surfaces; however, they have also been found to contribute to the pathogenesis of multiple autoimmune diseases and have been targeted therapeutically. Due to the role of Th17 cells in autoimmune pathogenesis, it is important to understand the factors that control Th17 development. Here we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of Th17 differentiation. Mice with T cell-specific deletion of
    MeSH term(s) Animals ; Cell Differentiation ; Colitis/immunology ; Colitis/pathology ; DNA, Intergenic/genetics ; Epigenesis, Genetic ; Histones/metabolism ; Interleukin-2/metabolism ; Lysine/metabolism ; Methylation ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell/metabolism ; Repressor Proteins/deficiency ; Repressor Proteins/metabolism ; Th17 Cells/cytology ; Th17 Cells/immunology
    Chemical Substances Atf7ip protein, mouse ; DNA, Intergenic ; Histones ; Interleukin-2 ; Receptors, Antigen, T-Cell ; Repressor Proteins ; Lysine (K3Z4F929H6)
    Language English
    Publishing date 2019-06-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20182316
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  5. Article: Analysis of pulmonary features and treatment approaches in the COPA syndrome.

    Tsui, Jessica L / Estrada, Oscar A / Deng, Zimu / Wang, Kristin M / Law, Christopher S / Elicker, Brett M / Jones, Kirk D / Dell, Sharon D / Gudmundsson, Gunnar / Hansdottir, Sif / Helfgott, Simon M / Volpi, Stefano / Gattorno, Marco / Waterfield, Michael R / Chan, Alice Y / Chung, Sharon A / Ley, Brett / Shum, Anthony K

    ERJ open research

    2018  Volume 4, Issue 2

    Abstract: The COPA syndrome is a monogenic, autoimmune lung and joint disorder first identified in 2015. This study sought to define the main pulmonary features of the COPA syndrome in an international cohort of patients, analyse patient responses to treatment and ...

    Abstract The COPA syndrome is a monogenic, autoimmune lung and joint disorder first identified in 2015. This study sought to define the main pulmonary features of the COPA syndrome in an international cohort of patients, analyse patient responses to treatment and highlight when genetic testing should be considered. We established a cohort of subjects (N=14) with COPA syndrome seen at multiple centres including the University of California, San Francisco, CA, USA. All subjects had one of the previously established mutations in the
    Language English
    Publishing date 2018-06-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2827830-6
    ISSN 2312-0541
    ISSN 2312-0541
    DOI 10.1183/23120541.00017-2018
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  6. Article: NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase.

    Waterfield, Michael R / Zhang, Minying / Norman, Lourdes P / Sun, Shao Cong

    Molecular cell

    2003  Volume 11, Issue 3, Page(s) 685–694

    Abstract: NF-kappaB family of transcription factors plays a pivotal role in regulation of immune and inflammatory responses. NF-kappaB is known to function by binding to the kappaB enhancer and directly activating target gene transcription. Here we demonstrate ... ...

    Abstract NF-kappaB family of transcription factors plays a pivotal role in regulation of immune and inflammatory responses. NF-kappaB is known to function by binding to the kappaB enhancer and directly activating target gene transcription. Here we demonstrate another function of NF-kappaB, in which the nfkappab1 gene product p105 regulates MAP kinase signaling triggered by the bacterial component lipopolysaccharide. p105 exerts this signaling function by controlling the stability and function of an upstream kinase, Tpl2. In macrophages, Tpl2 forms a stable and inactive complex with p105, and activation of Tpl2 involves its dissociation from p105 and subsequent degradation. Thus, p105 functions as a physiological partner and inhibitor of Tpl2, which provides an example of how a transcription factor component regulates upstream signaling events.
    MeSH term(s) Animals ; Cell Line ; Gene Expression Regulation, Enzymologic ; Humans ; Immunoblotting ; Lipopolysaccharides/metabolism ; MAP Kinase Kinase Kinases/metabolism ; MAP Kinase Signaling System ; Macrophages/metabolism ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Models, Biological ; NF-kappa B/metabolism ; NF-kappa B p50 Subunit ; Plasmids/metabolism ; Precipitin Tests ; Protein Binding ; Protein Precursors/metabolism ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/metabolism ; Retroviridae/genetics ; Signal Transduction ; Spleen/cytology ; Spleen/metabolism ; Time Factors ; Transcription, Genetic
    Chemical Substances Lipopolysaccharides ; NF-kappa B ; NF-kappa B p50 Subunit ; Protein Precursors ; Proto-Oncogene Proteins ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP3K8 protein, human (EC 2.7.11.25) ; Map3k8 protein, mouse (EC 2.7.11.25)
    Language English
    Publishing date 2003-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/s1097-2765(03)00070-4
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  7. Article ; Online: COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.

    Watkin, Levi B / Jessen, Birthe / Wiszniewski, Wojciech / Vece, Timothy J / Jan, Max / Sha, Youbao / Thamsen, Maike / Santos-Cortez, Regie L P / Lee, Kwanghyuk / Gambin, Tomasz / Forbes, Lisa R / Law, Christopher S / Stray-Pedersen, Asbjørg / Cheng, Mickie H / Mace, Emily M / Anderson, Mark S / Liu, Dongfang / Tang, Ling Fung / Nicholas, Sarah K /
    Nahmod, Karen / Makedonas, George / Canter, Debra L / Kwok, Pui-Yan / Hicks, John / Jones, Kirk D / Penney, Samantha / Jhangiani, Shalini N / Rosenblum, Michael D / Dell, Sharon D / Waterfield, Michael R / Papa, Feroz R / Muzny, Donna M / Zaitlen, Noah / Leal, Suzanne M / Gonzaga-Jauregui, Claudia / Boerwinkle, Eric / Eissa, N Tony / Gibbs, Richard A / Lupski, James R / Orange, Jordan S / Shum, Anthony K

    Nature genetics

    2015  Volume 47, Issue 6, Page(s) 654–660

    Abstract: Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity ... ...

    Abstract Unbiased genetic studies have uncovered surprising molecular mechanisms in human cellular immunity and autoimmunity. We performed whole-exome sequencing and targeted sequencing in five families with an apparent mendelian syndrome of autoimmunity characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease. We identified four unique deleterious variants in the COPA gene (encoding coatomer subunit α) affecting the same functional domain. Hypothesizing that mutant COPA leads to defective intracellular transport via coat protein complex I (COPI), we show that COPA variants impair binding to proteins targeted for retrograde Golgi-to-ER transport. Additionally, expression of mutant COPA results in ER stress and the upregulation of cytokines priming for a T helper type 17 (TH17) response. Patient-derived CD4(+) T cells also demonstrate significant skewing toward a TH17 phenotype that is implicated in autoimmunity. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease.
    MeSH term(s) Amino Acid Sequence ; Arthritis/genetics ; Autoimmune Diseases/genetics ; Child, Preschool ; Coatomer Protein/genetics ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Golgi Apparatus/metabolism ; HEK293 Cells ; Humans ; Infant ; Lod Score ; Lung Diseases, Interstitial/genetics ; Male ; Molecular Sequence Data ; Pedigree ; Protein Transport
    Chemical Substances Coatomer Protein
    Language English
    Publishing date 2015-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.3279
    Database MEDical Literature Analysis and Retrieval System OnLINE

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