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  1. Article ; Online: Introduction: thymus development and function in health and disease.

    Holländer, Georg A

    Seminars in immunopathology

    2021  Volume 43, Issue 1, Page(s) 1–3

    Language English
    Publishing date 2021-03-02
    Publishing country Germany
    Document type Editorial
    ZDB-ID 2316828-6
    ISSN 1863-2300 ; 1863-2297
    ISSN (online) 1863-2300
    ISSN 1863-2297
    DOI 10.1007/s00281-021-00841-4
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  2. Book: Immunologie

    Barthlott, Thomas / Holländer, Georg A.

    Grundlagen für Klinik und Praxis

    2006  

    Author's details Georg A. Holländer (Hrsg.). Unter Mitarb. von T. Barthlott
    Keywords Immunity ; Immune System ; Immunologie
    Subject Klinische Immunologie
    Language German
    Size IX, 291 S. : Ill., graph. Darst.
    Edition 1. Aufl.
    Publisher Elsevier, Urban & Fischer
    Publishing place München u.a.
    Publishing country Germany
    Document type Book
    HBZ-ID HT014525506
    ISBN 3-437-21301-6 ; 978-3-437-21301-4
    Database Catalogue ZB MED Medicine, Health

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    2006 A 131 order for loan Magazin
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  3. Article ; Online: Comment on "Identification of an Intronic Regulatory Element Necessary for Tissue-Specific Expression of

    Handel, Adam E / Holländer, Georg A

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Volume 203, Issue 9, Page(s) 2355

    MeSH term(s) Epithelial Cells ; Introns ; Regulatory Sequences, Nucleic Acid
    Language English
    Publishing date 2019-10-18
    Publishing country United States
    Document type Letter ; Comment
    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.1900948
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  4. Article ; Online: New developments in autism spectrum disorders. Interview by Dr. George Lundberg.

    Hollander, Eric

    Medscape journal of medicine

    2008  Volume 10, Issue 6, Page(s) 152

    MeSH term(s) Autistic Disorder/diagnosis ; Autistic Disorder/etiology ; Autistic Disorder/genetics ; Child Development Disorders, Pervasive/diagnosis ; Child Development Disorders, Pervasive/etiology ; Child Development Disorders, Pervasive/genetics ; Child, Preschool ; Humans
    Language English
    Publishing date 2008-06-27
    Publishing country United States
    Document type Interview
    ZDB-ID 2624206-0
    ISSN 1934-1997 ; 1934-1997
    ISSN (online) 1934-1997
    ISSN 1934-1997
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  5. Article ; Online: The role of thymic tolerance in CNS autoimmune disease.

    Handel, Adam E / Irani, Sarosh R / Holländer, Georg A

    Nature reviews. Neurology

    2018  Volume 14, Issue 12, Page(s) 723–734

    Abstract: The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for ...

    Abstract The contributions of the peripheral adaptive and innate immune systems to CNS autoimmunity have been extensively studied. However, the role of thymic selection in these conditions is much less well understood. The thymus is the primary lymphoid organ for the generation of T cells; thymic mechanisms ensure that cells with an overt autoreactive specificity are eliminated before they emigrate to the periphery and control the generation of thymic regulatory T cells. Evidence from animal studies demonstrates that thymic T cell selection is important for establishing tolerance to autoantigens. However, there is a considerable knowledge gap regarding the role of thymic selection in autoimmune conditions of the human CNS. In this Review, we critically examine the current body of experimental evidence for the contribution of thymic tolerance to CNS autoimmune diseases. An understanding of why dysfunction of either thymic or peripheral tolerance mechanisms rarely leads to CNS inflammation is currently lacking. We examine the potential of de novo T cell formation and thymic selection as novel therapeutic avenues and highlight areas for future study that are likely to make these targets the focus of future treatments.
    MeSH term(s) Animals ; Autoimmune Diseases of the Nervous System/immunology ; Autoimmune Diseases of the Nervous System/pathology ; Autoimmune Diseases of the Nervous System/physiopathology ; Humans ; Immune Tolerance/physiology ; T-Lymphocytes, Regulatory ; Thymus Gland/immunology ; Thymus Gland/pathology
    Language English
    Publishing date 2018-11-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2491514-2
    ISSN 1759-4766 ; 1759-4758
    ISSN (online) 1759-4766
    ISSN 1759-4758
    DOI 10.1038/s41582-018-0095-7
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  6. Article: Lymphoid reconstitution following hematopoietic stem cell transplantation. Of mice and men: progress made in HSCT immunobiology.

    Holländer, Georg A

    Seminars in immunopathology

    2008  Volume 30, Issue 4, Page(s) 369–370

    MeSH term(s) Animals ; Hematopoietic Stem Cell Transplantation ; Humans
    Language English
    Publishing date 2008-12
    Publishing country Germany
    Document type Introductory Journal Article
    ZDB-ID 2316828-6
    ISSN 1863-2300 ; 1863-2297
    ISSN (online) 1863-2300
    ISSN 1863-2297
    DOI 10.1007/s00281-008-0139-y
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  7. Article ; Online: RBFOX splicing factors contribute to a broad but selective recapitulation of peripheral tissue splicing patterns in the thymus.

    Jansen, Kathrin / Shikama-Dorn, Noriko / Attar, Moustafa / Maio, Stefano / Lopopolo, Maria / Buck, David / Holländer, Georg A / Sansom, Stephen N

    Genome research

    2021  Volume 31, Issue 11, Page(s) 2022–2034

    Abstract: Thymic epithelial cells (TEC) control the selection of a T cell repertoire reactive to pathogens but tolerant of self. This process is known to involve the promiscuous expression of virtually the entire protein-coding gene repertoire, but the extent to ... ...

    Abstract Thymic epithelial cells (TEC) control the selection of a T cell repertoire reactive to pathogens but tolerant of self. This process is known to involve the promiscuous expression of virtually the entire protein-coding gene repertoire, but the extent to which TEC recapitulate peripheral isoforms, and the mechanisms by which they do so, remain largely unknown. We performed the first assembly-based transcriptomic census of transcript structures and splicing factor (SF) expression in mouse medullary TEC (mTEC) and 21 peripheral tissues. Mature mTEC expressed 60.1% of all protein-coding transcripts, more than was detected in any of the peripheral tissues. However, for genes with tissue-restricted expression, mTEC produced fewer isoforms than did the relevant peripheral tissues. Analysis of exon inclusion revealed an absence of brain-specific microexons in mTEC. We did not find unusual numbers of novel transcripts in TEC, and we show that
    MeSH term(s) Animals ; Cell Differentiation/genetics ; Epithelial Cells/metabolism ; Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; RNA Splicing ; RNA Splicing Factors/genetics ; RNA Splicing Factors/metabolism ; Thymus Gland/metabolism ; Transcriptome
    Chemical Substances RNA Splicing Factors ; Rbfox2 protein, mouse
    Language English
    Publishing date 2021-10-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.275245.121
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  8. Article: Claudins provide a breath of fresh Aire.

    Holländer, Georg A

    Nature immunology

    2007  Volume 8, Issue 3, Page(s) 234–236

    MeSH term(s) Animals ; Antigen Presentation/immunology ; Autoimmunity ; Cell Differentiation ; Cell Lineage/immunology ; Epithelial Cells/cytology ; Humans ; Immune Tolerance ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Models, Immunological ; Thymus Gland/cytology ; Thymus Gland/embryology ; Thymus Gland/growth & development ; Transcription Factors/immunology ; Transcription Factors/metabolism ; AIRE Protein
    Chemical Substances Membrane Proteins ; Transcription Factors
    Language English
    Publishing date 2007-01-19
    Publishing country United States
    Document type Comment ; News
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni0307-234
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  9. Article ; Online: Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells.

    Klein, Fabian / Veiga-Villauriz, Clara / Börsch, Anastasiya / Maio, Stefano / Palmer, Sam / Dhalla, Fatima / Handel, Adam E / Zuklys, Saulius / Calvo-Asensio, Irene / Musette, Lucas / Deadman, Mary E / White, Andrea J / Lucas, Beth / Anderson, Graham / Holländer, Georg A

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 4071

    Abstract: The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among ... ...

    Abstract The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells' RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes.
    MeSH term(s) Female ; Pregnancy ; Humans ; Epithelial Cells ; Cell Differentiation ; Thymocytes ; Cues ; RNA
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2023-07-10
    Publishing country England
    Document type Journal Article ; 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/s41467-023-39722-9
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  10. Article ; Online: Biologically indeterminate yet ordered promiscuous gene expression in single medullary thymic epithelial cells.

    Dhalla, Fatima / Baran-Gale, Jeanette / Maio, Stefano / Chappell, Lia / Holländer, Georg A / Ponting, Chris P

    The EMBO journal

    2019  Volume 39, Issue 1, Page(s) e101828

    Abstract: To induce central T-cell tolerance, medullary thymic epithelial cells (mTEC) collectively express most protein-coding genes, thereby presenting an extensive library of tissue-restricted antigens (TRAs). To resolve mTEC diversity and whether promiscuous ... ...

    Abstract To induce central T-cell tolerance, medullary thymic epithelial cells (mTEC) collectively express most protein-coding genes, thereby presenting an extensive library of tissue-restricted antigens (TRAs). To resolve mTEC diversity and whether promiscuous gene expression (PGE) is stochastic or coordinated, we sequenced transcriptomes of 6,894 single mTEC, enriching for 1,795 rare cells expressing either of two TRAs, TSPAN8 or GP2. Transcriptional heterogeneity allowed partitioning of mTEC into 15 reproducible subpopulations representing distinct maturational trajectories, stages and subtypes, including novel mTEC subsets, such as chemokine-expressing and ciliated TEC, which warrant further characterisation. Unexpectedly, 50 modules of genes were robustly defined each showing patterns of co-expression within individual cells, which were mainly not explicable by chromosomal location, biological pathway or tissue specificity. Further, TSPAN8
    MeSH term(s) Animals ; Biomarkers/analysis ; Biomarkers/metabolism ; Cell Differentiation ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Female ; Gene Expression Profiling ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Organ Specificity ; Single-Cell Analysis/methods ; Thymus Gland/cytology ; Thymus Gland/metabolism ; Transcriptome
    Chemical Substances Biomarkers
    Language English
    Publishing date 2019-10-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2019101828
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