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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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Article: Thymus Extracellular Matrix-Derived Scaffolds Support Graft-Resident Thymopoiesis and Long-Term In Vitro Culture of Adult Thymic Epithelial Cells.

Asnaghi, M Adelaide / Barthlott, Thomas / Gullotta, Fabiana / Strusi, Valentina / Amovilli, Anna / Hafen, Katrin / Srivastava, Gitika / Oertle, Philipp / Toni, Roberto / Wendt, David / Holländer, Georg A / Martin, Ivan

Advanced functional materials

2021 Volume 31, Issue 20, Page(s) 2010747

Abstract: The thymus provides the physiological microenvironment critical for the development of T lymphocytes, the cells that orchestrate the adaptive immune system to generate an antigen-specific response. A diverse population of stroma cells provides surface- ... ...

Abstract	The thymus provides the physiological microenvironment critical for the development of T lymphocytes, the cells that orchestrate the adaptive immune system to generate an antigen-specific response. A diverse population of stroma cells provides surface-bound and soluble molecules that orchestrate the intrathymic maturation and selection of developing T cells. Forming an intricate 3D architecture, thymic epithelial cells (TEC) represent the most abundant and important constituent of the thymic stroma. Effective models for in and ex vivo use of adult TEC are still wanting, limiting the engineering of functional thymic organoids and the understanding of the development of a competent immune system. Here a 3D scaffold is developed based on decellularized thymic tissue capable of supporting in vitro and in vivo thymopoiesis by both fetal and adult TEC. For the first time, direct evidences of feasibility for sustained graft-resident T-cell development using adult TEC as input are provided. Moreover, the scaffold supports prolonged in vitro culture of adult TEC, with a retained expression of the master regulator Foxn1. The success of engineering a thymic scaffold that sustains adult TEC function provides unprecedented opportunities to investigate thymus development and physiology and to design and implement novel strategies for thymus replacement therapies.
Language	English
Publishing date	2021-03-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2039420-2
ISSN	1616-3028 ; 1616-301X
ISSN (online)	1616-3028
ISSN	1616-301X
DOI	10.1002/adfm.202010747
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2.

Barthlott, Thomas / Handel, Adam E / Teh, Hong Ying / Wirasinha, Rushika C / Hafen, Katrin / Žuklys, Saulius / Roch, Benoit / Orkin, Stuart H / de Villartay, Jean-Pierre / Daley, Stephen R / Holländer, Georg A

Nature communications

2021 Volume 12, Issue 1, Page(s) 3933

Abstract: Thymic T cell development and T cell receptor repertoire selection are dependent on essential molecular cues provided by thymic epithelial cells (TEC). TEC development and function are regulated by their epigenetic landscape, in which the repressive ... ...

Abstract	Thymic T cell development and T cell receptor repertoire selection are dependent on essential molecular cues provided by thymic epithelial cells (TEC). TEC development and function are regulated by their epigenetic landscape, in which the repressive H3K27me3 epigenetic marks are catalyzed by polycomb repressive complex 2 (PRC2). Here we show that a TEC-targeted deficiency of PRC2 function results in a hypoplastic thymus with reduced ability to express antigens and select a normal repertoire of T cells. The absence of PRC2 activity reveals a transcriptomically distinct medullary TEC lineage that incompletely off-sets the shortage of canonically-derived medullary TEC whereas cortical TEC numbers remain unchanged. This alternative TEC development is associated with the generation of reduced TCR diversity. Hence, normal PRC2 activity and placement of H3K27me3 marks are required for TEC lineage differentiation and function and, in their absence, the thymus is unable to compensate for the loss of a normal TEC scaffold.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation ; Cell Lineage ; Epigenesis, Genetic ; Epithelial Cells/cytology ; Epithelial Cells/physiology ; Female ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Polycomb Repressive Complex 2/genetics ; Polycomb Repressive Complex 2/metabolism ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes/cytology ; T-Lymphocytes/physiology ; Thymocytes/cytology ; Thymocytes/physiology ; Thymus Gland/cytology ; Thymus Gland/physiology ; Mice
Chemical Substances	Eed protein, mouse ; Receptors, Antigen, T-Cell ; Polycomb Repressive Complex 2 (EC 2.1.1.43)
Language	English
Publishing date	2021-06-24
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/s41467-021-24158-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Differential Response of Mouse Thymic Epithelial Cell Types to Ionizing Radiation-Induced DNA Damage.

Calvo-Asensio, Irene / Barthlott, Thomas / von Muenchow, Lilly / Lowndes, Noel F / Ceredig, Rhodri

Frontiers in immunology

2017 Volume 8, Page(s) 418

Abstract: Thymic epithelial cells (TECs) are the main components of the thymic stroma that support and control T-cell development. Preparative regimens using DNA-damaging agents, such as total body irradiation and/or chemotherapeutic drugs, that are necessary ... ...

Abstract	Thymic epithelial cells (TECs) are the main components of the thymic stroma that support and control T-cell development. Preparative regimens using DNA-damaging agents, such as total body irradiation and/or chemotherapeutic drugs, that are necessary prior to bone marrow transplantation (BMT) have profound deleterious effects on the hematopoietic system, including the thymic stroma, which may be one of the main causes for the prolonged periods of T-cell deficiency and the inefficient T cell reconstitution that are common following BMT. The DNA damage response (DDR) is a complex signaling network that allows cells to respond to all sorts of genotoxic insults. Hypoxia is known to modulate the DDR and play a role affecting the survival capacity of different cell types. In this study, we have characterized in detail the DDR of cortical and medullary TEC lines and their response to ionizing radiation, as well as the effects of hypoxia on their DDR. Although both mTECs and cTECs display relatively high radio-resistance, mTEC cells have an increased survival capacity to ionizing radiation (IR)-induced DNA damage, and hypoxia specifically decreases the radio-resistance of mTECs by upregulating the expression of the pro-apoptotic factor Bim. Analysis of the expression of TEC functional factors by primary mouse TECs showed a marked decrease of highly important genes for TEC function and confirmed cTECs as the most affected cell type by IR. These findings have important implications for improving the outcomes of BMT and promoting successful T cell reconstitution.
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.00418
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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	Immunologie
Language	German
Size	IX, 291 S., Ill., graph. Darst., 27 cm
Edition	1. Aufl.
Publisher	Elsevier, Urban & Fischer
Publishing place	München u.a.
Document type	Book
ISBN	3437213016 ; 9783437213014
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Cell Growth Dynamics in Embryonic and Adult Mouse Thyroid Revealed by a Novel Approach to Detect Thyroid Gland Subpopulations.

Gawade, Sanjay / Mayer, Carlos / Hafen, Katrin / Barthlott, Thomas / Krenger, Werner / Szinnai, Gabor

Thyroid : official journal of the American Thyroid Association

2016 Volume 26, Issue 4, Page(s) 591–599

Abstract: Background: The thyroid is composed of endocrine epithelial cells, blood vessels, and mesenchyme. However, no data exist thus far on absolute cell numbers, relative distribution, and proliferation of the different cell populations in the developing and ... ...

Abstract	Background: The thyroid is composed of endocrine epithelial cells, blood vessels, and mesenchyme. However, no data exist thus far on absolute cell numbers, relative distribution, and proliferation of the different cell populations in the developing and mature thyroid. The aim of this study was therefore to establish a flow cytometry protocol that allows detection and quantification of discrete cell populations in embryonic and adult murine thyroid tissues. Methods: Cell-type anti-mouse specific antibodies were used for erythroid cells (Ter119), hematopoietic cells (CD45), epithelial cells (EpCam/CD326, E-cadherin/CD324), thyroid follicular cells and C-cells (Nkx2-1), endothelial cells (Pecam/CD31, Icam-1/CD54), and fibroblasts (PDGFRa/CD140a). Proliferating cells were detected after labeling with 5-bromo-2'-deoxyuridine (BrdU). For flow cytometry analyses, micro-dissected embryonic (E) and adult thyroids were pooled (E13.5, n = 25; E15.5, n = 15; E17.5, n = 15; adult, n = 4) in one sample. Results: The absolute parenchymal cell numbers per mouse thyroid (M ± SD), excluding the large number of CD45(+) and Ter119(+) cells, increased from 7425 ± 1338 at E13.5 to 271,561 ± 22,325 in adult tissues. As expected, Nkx2-1(+) cells represented the largest cell population in adult tissues (61.2 ± 1.1%). Surprisingly, at all three embryonic stages analyzed, thyroid follicular cells and C-cells accounted only for a small percentage of the total thyroid cell mass (between 4.7 ± 0.4% and 9.4 ± 1.6%). In contrast, the largest cell population at all three embryonic stages was identified as PDGFRa/CD140a(+) fibroblasts (61.4 ± 0.4% to 77.3 ± 1.1%). However, these cells represented the smallest population in adult tissues (5.2 ± 0.8%). Pecam/CD31(+) endothelial cells increased from E13.5 to E15.5 from 3.7 ± 0.8% to 8.5 ± 3.0%, then remained stable at E17.5 and adult tissues. Proliferation rates were sizable during the entire organogenesis but differed between cell populations, with distinct proliferative peaks at E13.5 in epithelial cells (32.7 ± 0.6% BrdU(+) cells), and at E15.5 in endothelial cells (22.4 ± 2.4% BrdU(+) cells). Fibroblasts showed a constant proliferation rate in embryonic tissues. In adult tissues, BrdU(+) cells were between 0.1% and 0.4% in all cell types. Conclusions: Using a novel flow cytometry-based method, a previously unobserved highly dynamic growth pattern of thyroid cell populations during embryogenesis was uncovered. This approach will provide a useful new tool for cell function analyses in murine thyroid disease models.
MeSH term(s)	Animals ; Antibodies/chemistry ; Cell Differentiation ; Cell Proliferation ; Cell Separation ; Epithelial Cells/cytology ; Female ; Fibroblasts/cytology ; Flow Cytometry ; Mesoderm/cytology ; Mice ; Thyroid Gland/cytology ; Thyroid Gland/embryology
Chemical Substances	Antibodies
Language	English
Publishing date	2016-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2015.0523
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The concept of space and competition in immune regulation.

Stockinger, Brigitta / Barthlott, Thomas / Kassiotis, George

Immunology

2004 Volume 111, Issue 3, Page(s) 241–247

MeSH term(s)	Animals ; Antigens, CD/immunology ; Autoimmunity/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cell Division/immunology ; Homeostasis/immunology ; Humans ; Immunity, Cellular/immunology ; Immunologic Memory/immunology ; Major Histocompatibility Complex/immunology ; Mice ; Receptors, Interleukin-2/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes/immunology ; Thymus Gland/immunology
Chemical Substances	Antigens, CD ; Receptors, Interleukin-2
Language	English
Publishing date	2004-02-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/j.1365-2567.2004.01831.x
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Article: A short primer on early molecular and cellular events in thymus organogenesis and replacement.

Barthlott, Thomas / Keller, Marcel P / Krenger, Werner / Holländer, Georg A

Swiss medical weekly

2007 Volume 137 Suppl 155, Page(s) 9S–13S

Abstract: Haematopoietic precursors have to undergo a complex series of maturational steps in the thymus before they exit into the periphery as functional T lymphocytes. Thymic stroma cells, the majority being of epithelial origin, provide the functional partners ... ...

Abstract	Haematopoietic precursors have to undergo a complex series of maturational steps in the thymus before they exit into the periphery as functional T lymphocytes. Thymic stroma cells, the majority being of epithelial origin, provide the functional partners for the maturational progression along this differentiation pathway. Here we review some of the molecular and cellular mechanisms that account for thymus organogenesis and discuss a strategy to use thymic epithelial precursor cells for the regeneration of the thymic microenvironment.
Language	English
Publishing date	2007-03-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036179-8
ISSN	1424-3997 ; 1424-7860
ISSN (online)	1424-3997
ISSN	1424-7860
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Article ; Online: Foxn1 regulates key target genes essential for T cell development in postnatal thymic epithelial cells.

Žuklys, Saulius / Handel, Adam / Zhanybekova, Saule / Govani, Fatima / Keller, Marcel / Maio, Stefano / Mayer, Carlos E / Teh, Hong Ying / Hafen, Katrin / Gallone, Giuseppe / Barthlott, Thomas / Ponting, Chris P / Holländer, Georg A

Nature immunology

2016 Volume 17, Issue 10, Page(s) 1206–1215

Abstract: Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin ... ...

Abstract	Thymic epithelial cell differentiation, growth and function depend on the expression of the transcription factor Foxn1; however, its target genes have never been physically identified. Using static and inducible genetic model systems and chromatin studies, we developed a genome-wide map of direct Foxn1 target genes for postnatal thymic epithelia and defined the Foxn1 binding motif. We determined the function of Foxn1 in these cells and found that, in addition to the transcriptional control of genes involved in the attraction and lineage commitment of T cell precursors, Foxn1 regulates the expression of genes involved in antigen processing and thymocyte selection. Thus, critical events in thymic lympho-stromal cross-talk and T cell selection are indispensably choreographed by Foxn1.
MeSH term(s)	Animals ; Antigen Presentation/genetics ; Cell Communication ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Cells, Cultured ; Clonal Selection, Antigen-Mediated/genetics ; Epithelial Cells/physiology ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation ; Genome/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mice, Transgenic ; Precursor Cells, T-Lymphoid/physiology ; T-Lymphocytes/physiology ; Thymus Gland/physiology
Chemical Substances	Forkhead Transcription Factors ; Whn protein
Language	English
Publishing date	2016-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/ni.3537
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Article: A short primer on early molecular and cellular events in thymus organogenesis and replacement.

Barthlott, Thomas / Keller, Marcel P / Krenger, Werner / Holländer, Georg A

Swiss medical weekly

2006 Volume 136, Issue 23-24, Page(s) 365–369

Abstract	Haematopoietic precursors have to undergo a complex series of maturational steps in the thymus before they exit into the periphery as functional T lymphocytes. Thymic stroma cells, the majority being of epithelial origin, provide the functional partners for the maturational progression along this differentiation pathway. Here we review some of the molecular and cellular mechanisms that account for thymus organogenesis and discuss a strategy to use thymic epithelial precursor cells for the regeneration of the thymic microenvironment.
MeSH term(s)	Autoantigens ; Epithelial Cells/cytology ; Hematopoietic Stem Cells/cytology ; Humans ; Organogenesis ; Regeneration ; Signal Transduction ; Stromal Cells/cytology ; T-Lymphocytes/cytology ; T-Lymphocytes/immunology ; Thymus Gland/cytology ; Thymus Gland/immunology
Chemical Substances	Autoantigens
Language	English
Publishing date	2006-06-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036179-8
ISSN	1424-3997 ; 1424-7860
ISSN (online)	1424-3997
ISSN	1424-7860
DOI	10.4414/smw.2006.11401
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