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  1. Artikel ; Online: The Effects of Androgens on T Cells: Clues to Female Predominance in Autoimmune Liver Diseases?

    Henze, Lara / Schwinge, Dorothee / Schramm, Christoph

    Frontiers in immunology

    2020  Band 11, Seite(n) 1567

    Abstract: The immune system responds differently in women and in men. Generally speaking, adult females show stronger innate and adaptive immune responses than males. This results in lower risk of developing most of the infectious diseases and a better ability to ... ...

    Abstract The immune system responds differently in women and in men. Generally speaking, adult females show stronger innate and adaptive immune responses than males. This results in lower risk of developing most of the infectious diseases and a better ability to clear viral infection in women (1-5). On the other hand, women are at increased risk of developing autoimmune diseases (AID) such as rheumatoid arthritis, multiple sclerosis (MS), systemic lupus erythematosus (SLE), Sjögren's syndrome, and the autoimmune liver diseases autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) (6). Factors contributing to the female sex bias in autoimmune diseases include environmental exposure, e.g., microbiome, behavior, and genetics including X chromosomal inactivation of genes. Several lines of evidence and clinical observations clearly indicate that sex hormones contribute significantly to disease pathogenesis, and the role of estrogen in autoimmune diseases has been extensively studied. In many of these diseases, including the autoimmune liver diseases, T cells are thought to play an important pathogenetic role. We will use this mini-review to focus on the effects of androgens on T cells and how the two major androgens, testosterone and dihydrotestosterone, potentially contribute to the pathogenesis of autoimmune liver diseases (AILD).
    Mesh-Begriff(e) Androgens/metabolism ; Androgens/pharmacology ; Animals ; Autoimmune Diseases/etiology ; Autoimmune Diseases/metabolism ; Autoimmune Diseases/pathology ; Cell Membrane/metabolism ; Cytosol/metabolism ; Disease Models, Animal ; Female ; Humans ; Immunomodulation/drug effects ; Liver Diseases/etiology ; Liver Diseases/metabolism ; Liver Diseases/pathology ; Male ; Receptors, Androgen/metabolism ; Sex Factors ; Signal Transduction ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
    Chemische Substanzen Androgens ; Receptors, Androgen
    Sprache Englisch
    Erscheinungsdatum 2020-07-29
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.01567
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Human γδ T cell identification from single-cell RNA sequencing datasets by modular TCR expression.

    Song, Zheng / Henze, Lara / Casar, Christian / Schwinge, Dorothee / Schramm, Christoph / Fuss, Johannes / Tan, Likai / Prinz, Immo

    Journal of leukocyte biology

    2023  Band 114, Heft 6, Seite(n) 630–638

    Abstract: Accurately identifying γδ T cells in large single-cell RNA sequencing (scRNA-seq) datasets without additional single-cell γδ T cell receptor sequencing (sc-γδTCR-seq) or CITE-seq (cellular indexing of transcriptomes and epitopes sequencing) data remains ... ...

    Abstract Accurately identifying γδ T cells in large single-cell RNA sequencing (scRNA-seq) datasets without additional single-cell γδ T cell receptor sequencing (sc-γδTCR-seq) or CITE-seq (cellular indexing of transcriptomes and epitopes sequencing) data remains challenging. In this study, we developed a TCR module scoring strategy for human γδ T cell identification (i.e. based on modular gene expression of constant and variable TRA/TRB and TRD genes). We evaluated our method using 5' scRNA-seq datasets comprising both sc-αβTCR-seq and sc-γδTCR-seq as references and demonstrated that it can identify γδ T cells in scRNA-seq datasets with high sensitivity and accuracy. We observed a stable performance of this strategy across datasets from different tissues and different subtypes of γδ T cells. Thus, we propose this analysis method, based on TCR gene module scores, as a standardized tool for identifying and reanalyzing γδ T cells from 5'-end scRNA-seq datasets.
    Mesh-Begriff(e) Humans ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Intraepithelial Lymphocytes ; Transcriptome ; Sequence Analysis, RNA ; Single-Cell Analysis/methods
    Chemische Substanzen Receptors, Antigen, T-Cell, gamma-delta
    Sprache Englisch
    Erscheinungsdatum 2023-07-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1093/jleuko/qiad069
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Buch ; Online ; Dissertation / Habilitation: Testosterone: impact on peripheral human T cells in health and autoimmunity

    Henze, Lara [Verfasser] / Schramm, Christoph [Akademischer Betreuer]

    2021  

    Verfasserangabe Lara Henze ; Betreuer: Christoph Schramm
    Schlagwörter Biowissenschaften, Biologie ; Life Science, Biology
    Thema/Rubrik (Code) sg570
    Sprache Englisch
    Verlag Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky
    Erscheinungsort Hamburg
    Dokumenttyp Buch ; Online ; Dissertation / Habilitation
    Datenquelle Digitale Dissertationen im Internet

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  4. Artikel ; Konferenzbeitrag: [Titelangabe fehlt]

    Henze, Lara / Stein, Stephanie / Meyer, Jasper / Poch, Tobias / Krause, Jenny / Casar, Christian / Fuß, Johannes / Renné, Thomas / Schwinge, Dorothee / Schramm, Christoph

    Zeitschrift für Gastroenterologie

    2023  Band 61, Heft 01

    Veranstaltung/Kongress 39. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Bochum, 2023-01-27
    Sprache Deutsch
    Erscheinungsdatum 2023-01-01
    Verlag Georg Thieme Verlag
    Erscheinungsort Stuttgart ; New York
    Dokumenttyp Artikel ; Konferenzbeitrag
    ZDB-ID 201387-3
    ISSN 1439-7803 ; 0044-2771 ; 0172-8504
    ISSN (online) 1439-7803
    ISSN 0044-2771 ; 0172-8504
    DOI 10.1055/s-0042-1760069
    Datenquelle Thieme Verlag

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  5. Artikel ; Konferenzbeitrag: Testosterone as modulator of immune responses in female hepatic autoimmunity

    Will, Nico / Henze, Lara / Casar, Christian / Haas, Victor / Meyer, Jasper / Lee, Dakyung / Stein, Stephanie / Poch, Tobias / Krause, Jenny / Fuß, Johannes / Kulle, Elexandra E. / Holterhus, Paul-Martin / Huber, Samuel / Lohse, Ansgar W. / Schwinge, Dorothee / Schramm, Christoph

    Zeitschrift für Gastroenterologie

    2024  Band 62, Heft 01

    Veranstaltung/Kongress 40. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Haus der Technik e.V., Essen, 2024-01-26
    Sprache Deutsch
    Erscheinungsdatum 2024-01-01
    Verlag Georg Thieme Verlag
    Erscheinungsort Stuttgart ; New York
    Dokumenttyp Artikel ; Konferenzbeitrag
    ZDB-ID 201387-3
    ISSN 1439-7803 ; 0044-2771 ; 0172-8504
    ISSN (online) 1439-7803
    ISSN 0044-2771 ; 0172-8504
    DOI 10.1055/s-0043-1777496
    Datenquelle Thieme Verlag

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  6. Artikel ; Online: A prospective pilot study of a gluten-free diet for primary sclerosing cholangitis and associated colitis.

    Liwinski, Timur / Hübener, Sina / Henze, Lara / Hübener, Peter / Heinemann, Melina / Tetzlaff, Marcus / Hiller, Marie I / Jagemann, Bettina / Surabattula, Rambabu / Leeming, Diana / Karsdal, Morten / Monguzzi, Erika / Schachschal, Guido / Rösch, Thomas / Bang, Corinna / Franke, Andre / Lohse, Ansgar W / Schuppan, Detlef / Schramm, Christoph

    Alimentary pharmacology & therapeutics

    2022  Band 57, Heft 2, Seite(n) 224–236

    Abstract: Background: Primary sclerosing cholangitis (PSC) is a progressive bile duct disease associated with inflammatory bowel disease (PSC-IBD).: Aim: To investigate whether patients with PSC-IBD benefit from a gluten-free and amylase trypsin inhibitor (ATI) ...

    Abstract Background: Primary sclerosing cholangitis (PSC) is a progressive bile duct disease associated with inflammatory bowel disease (PSC-IBD).
    Aim: To investigate whether patients with PSC-IBD benefit from a gluten-free and amylase trypsin inhibitor (ATI)-free diet (GFD).
    Methods: We performed a prospective clinical pilot study administering an eight-week GFD. The primary outcomes were colonic inflammation assessed by proctosigmoidoscopy, and liver stiffness (surrogate for fibrosis, inflammation and cholestasis) measured by transient elastography before and after GFD. Amongst the secondary (exploratory) outcomes were colonic mucosal and serum cytokine/chemokine changes, the intestinal microbiome and transcriptome dynamics, and shifts in serum markers of hepatic fibrogenesis.
    Results: Fifteen patients with PSC-IBD completed the study. The study did not meet its primary outcome: the endoscopic score and liver stiffness remained unchanged. However, the expression of pro-inflammatory mucosal cytokines and chemokines such as IL6, IL8, CCL2, and TNFα was significantly down-regulated. Two critical markers of liver fibrosis and matrix remodelling, thrombospondin-2 and -4, decreased significantly. The microbiota composition changed slightly, including a decrease in the pathogen Romboutsia ilealis. The intestinal transcriptome indicated a gut barrier improvement. Pruritus, fatigue, overall well-being, faecal calprotectin levels, and serum alkaline phosphatase did not change significantly.
    Conclusions: This study did not demonstrate a clinical improvement with short-term GFD in patients with PSC-IBD. However, a gluten/ATI-free diet may improve biomarkers of intestinal inflammation and barrier function in these patients with associated changes in the enteric microbiota. Further investigation of the therapeutic potential of the GFD in PSC-IBD is warranted.
    Mesh-Begriff(e) Humans ; Pilot Projects ; Cholangitis, Sclerosing/complications ; Prospective Studies ; Diet, Gluten-Free ; Inflammatory Bowel Diseases/complications ; Colitis ; Inflammation/complications
    Sprache Englisch
    Erscheinungsdatum 2022-10-20
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639012-2
    ISSN 1365-2036 ; 0269-2813 ; 0953-0673
    ISSN (online) 1365-2036
    ISSN 0269-2813 ; 0953-0673
    DOI 10.1111/apt.17256
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: TNF-Producing Th1 Cells Are Selectively Expanded in Liver Infiltrates of Patients with Autoimmune Hepatitis.

    Bovensiepen, Claudia S / Schakat, Miriam / Sebode, Marcial / Zenouzi, Roman / Hartl, Johannes / Peiseler, Moritz / Li, Jun / Henze, Lara / Woestemeier, Anna / Schramm, Christoph / Lohse, Ansgar W / Herkel, Johannes / Weiler-Normann, Christina

    Journal of immunology (Baltimore, Md. : 1950)

    2019  Band 203, Heft 12, Seite(n) 3148–3156

    Abstract: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that is believed to be driven by a ... ...

    Abstract Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that is believed to be driven by a CD4
    Mesh-Begriff(e) Adult ; Aged ; Amino Acyl-tRNA Synthetases/immunology ; Autoantigens/immunology ; Biomarkers ; Cytokines/biosynthesis ; Cytokines/genetics ; Female ; Gene Expression ; Hepatitis, Autoimmune/diagnosis ; Hepatitis, Autoimmune/etiology ; Hepatitis, Autoimmune/metabolism ; Humans ; Liver/immunology ; Liver/innervation ; Liver/metabolism ; Liver/pathology ; Liver Function Tests ; Lymphocyte Activation ; Lymphocyte Count ; Male ; Middle Aged ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Tumor Necrosis Factors/biosynthesis
    Chemische Substanzen Autoantigens ; Biomarkers ; Cytokines ; Tumor Necrosis Factors ; Amino Acyl-tRNA Synthetases (EC 6.1.1.-) ; O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, human (EC 6.1.1.-)
    Sprache Englisch
    Erscheinungsdatum 2019-11-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; 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.1900124
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: IL-17A/F enable cholangiocytes to restrict T cell-driven experimental cholangitis by upregulating PD-L1 expression.

    Stein, Stephanie / Henze, Lara / Poch, Tobias / Carambia, Antonella / Krech, Till / Preti, Max / Schuran, Fenja Amrei / Reich, Maria / Keitel, Verena / Fiorotto, Romina / Strazzabosco, Mario / Fischer, Lutz / Li, Jun / Müller, Luisa Marie / Wagner, Jonas / Gagliani, Nicola / Herkel, Johannes / Schwinge, Dorothee / Schramm, Christoph

    Journal of hepatology

    2020  Band 74, Heft 4, Seite(n) 919–930

    Abstract: Background & aims: IL-17A-producing T cells are present in autoimmune cholestatic liver diseases; however, little is known about the contribution of IL-17 to periductal immune responses. Herein, we investigated the role of IL-17 produced by antigen- ... ...

    Abstract Background & aims: IL-17A-producing T cells are present in autoimmune cholestatic liver diseases; however, little is known about the contribution of IL-17 to periductal immune responses. Herein, we investigated the role of IL-17 produced by antigen-specific CD8
    Methods: K14-OVAp mice express a major histocompatibility complex I-restricted ovalbumin (OVA) peptide sequence (SIINFEKL) on cholangiocytes. Cholangitis was induced by the adoptive transfer of transgenic OVA-specific ovalbumin transgene (OT)-1 CD8
    Results: Transfer of OVA-specific OT-1
    Conclusions: We demonstrate that by upregulating PD-L1 on cholangiocytes, IL-17 has an important role in restricting cholangitis and protecting against CD8
    Lay summary: IL-17 is assumed to be a driver of inflammation in several autoimmune diseases, such as psoriasis. IL-17 is also present in inflammatory diseases of the bile duct, but its role in these conditions is not clear, as the effects of IL-17 depend on the context of its expression. Herein, we investigated the role of IL-17 in an experimental autoimmune cholangitis mouse model, and we identified an important protective effect of IL-17 on cholangiocytes, enabling them to downregulate bile duct inflammation via checkpoint inhibitor PD-L1.
    Mesh-Begriff(e) Animals ; Autoimmune Diseases/immunology ; Autoimmune Diseases/pathology ; B7-H1 Antigen/metabolism ; Bile Ducts/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cholangitis/immunology ; Cholangitis/pathology ; Disease Models, Animal ; Gene Expression Regulation/physiology ; Humans ; Interleukin-17/immunology ; Mice ; Mice, Transgenic ; Organoids ; Ovalbumin/genetics ; Peptide Fragments/genetics
    Chemische Substanzen B7-H1 Antigen ; CD274 protein, human ; Cd274 protein, mouse ; IL17A protein, human ; Il17a protein, mouse ; Interleukin-17 ; OVA-8 ; Peptide Fragments ; Ovalbumin (9006-59-1)
    Sprache Englisch
    Erscheinungsdatum 2020-11-13
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 605953-3
    ISSN 1600-0641 ; 0168-8278
    ISSN (online) 1600-0641
    ISSN 0168-8278
    DOI 10.1016/j.jhep.2020.10.035
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Monocytes as Potential Mediators of Pathogen-Induced T-Helper 17 Differentiation in Patients With Primary Sclerosing Cholangitis (PSC).

    Kunzmann, Lilly Kristin / Schoknecht, Tanja / Poch, Tobias / Henze, Lara / Stein, Stephanie / Kriz, Marvin / Grewe, Ilka / Preti, Max / Hartl, Johannes / Pannicke, Nadine / Peiseler, Moritz / Sebode, Marcial / Zenouzi, Roman / Horvatits, Thomas / Böttcher, Marius / Petersen, Britt-Sabina / Weiler-Normann, Christina / Hess, Leonard U / Ahrenstorf, Annika Elise /
    Lunemann, Sebastian / Martrus, Gloria / Fischer, Lutz / Li, Jun / Carambia, Antonella / Kluwe, Johannes / Huber, Samuel / Lohse, Ansgar W / Franke, Andre / Herkel, Johannes / Schramm, Christoph / Schwinge, Dorothee

    Hepatology (Baltimore, Md.)

    2020  Band 72, Heft 4, Seite(n) 1310–1326

    Abstract: Background and aims: T cells from patients with primary sclerosing cholangitis (PSC) show a prominent interleukin (IL)-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant T-helper 17 (Th17) response in PSC are not ... ...

    Abstract Background and aims: T cells from patients with primary sclerosing cholangitis (PSC) show a prominent interleukin (IL)-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant T-helper 17 (Th17) response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T-cell response toward Th17.
    Approach and results: Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using transwell experiments with cholangiocytes. Cytokine production was measured using flow cytometry, enzyme-linked immunosorbent assay, RNA in situ hybridization, and quantitative real-time PCR. Genetic polymorphisms were obtained from ImmunoChip analysis. Following ex vivo stimulation with phorbol myristate acetate/ionomycin, PSC patients showed significantly increased numbers of IL-17A-producing peripheral blood CD4
    Conclusions: PSC patients show increased Th17 differentiation already in vivo. Microbe-stimulated monocytes drive Th17 differentiation in vitro and induce cholangiocytes to produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.
    Mesh-Begriff(e) Adolescent ; Adult ; Aged ; Aged, 80 and over ; CARD Signaling Adaptor Proteins/genetics ; Cell Differentiation ; Chemokines/biosynthesis ; Cholangitis, Sclerosing/immunology ; Female ; Humans ; Interleukin-1beta/physiology ; Interleukins/genetics ; Liver Cirrhosis/immunology ; Male ; Middle Aged ; Monocytes/physiology ; Th17 Cells/cytology ; Young Adult
    Chemische Substanzen CARD Signaling Adaptor Proteins ; CARD9 protein, human ; Chemokines ; Interleukin-1beta ; Interleukins ; interleukin-21 (MKM3CA6LT1)
    Sprache Englisch
    Erscheinungsdatum 2020-10-08
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604603-4
    ISSN 1527-3350 ; 0270-9139
    ISSN (online) 1527-3350
    ISSN 0270-9139
    DOI 10.1002/hep.31140
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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