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Author Ulrich Steinhoff

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Development of a new macrophage-specific TRAP mouse (MacTRAP) and definition of the renal macrophage translational signature.

Andreas Hofmeister, Maximilian C Thomaßen, Sabrina Markert, André Marquardt, Mathieu Preußner, Martin Rußwurm, Ralph T Schermuly, Ulrich Steinhoff, Hermann-Josef Gröne, Joachim Hoyer, Benjamin D Humphreys, Ivica Grgic,

Tissue macrophages play an important role in organ homeostasis, immunity and the pathogenesis of various inflammation-driven diseases. One major challenge has been to selectively study resident macrophages in highly heterogeneous organs such as kidney. To address this problem, we adopted a Translational Ribosome Affinity Purification (TRAP)- approach and designed a ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):7519]

Cited: 0 times

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The NF-κB transcription factor c-Rel controls host defense against Citrobacter rodentium.

Maik Luu, Rossana Romero, Jasmin Bazant, Elfadil Abass, Sabrina Hartmann, Hanna Leister, Florence Fischer, Rouzbeh Mahdavi, Carlos Plaza-Sirvent, Ingo Schmitz, Ulrich Steinhoff, Alexander Visekruna,

Mice lacking CD4+ T cells or B cells are highly susceptible to Citrobacter rodentium infection. In this study, we show that the activity of the transcription factor c-Rel in lymphocytes is crucial for clearance of C. rodentium. Mice deficient for c-Rel fail to generate protective antibodies and to eradicate the ... Read more >>

Eur. J. Immunol. (European journal of immunology)
[2020, 50(2):292-294]

Cited: 0 times

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Intestinal development and homeostasis require activation and apoptosis of diet-reactive T cells.

Alexander Visekruna, Sabrina Hartmann, Yasmina Rodriguez Sillke, Rainer Glauben, Florence Fischer, Hartmann Raifer, Hans Mollenkopf, Wilhelm Bertrams, Bernd Schmeck, Matthias Klein, Axel Pagenstecher, Michael Lohoff, Ralf Jacob, Oliver Pabst, Paul William Bland, Maik Luu, Rossana Romero, Britta Siegmund, Krishnaraj Rajalingam, Ulrich Steinhoff,

The impact of food antigens on intestinal homeostasis and immune function is poorly understood. Here, we explored the impact of dietary antigens on the phenotype and fate of intestinal T cells. Physiological uptake of dietary proteins generated a highly activated CD44+Helios+CD4+ T cell population predominantly in Peyer patches. These cells ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2019, 129(5):1972-1983]

Cited: 0 times

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The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes.

Maik Luu, Sabine Pautz, Vanessa Kohl, Rajeev Singh, Rossana Romero, Sébastien Lucas, Jörg Hofmann, Hartmann Raifer, Niyati Vachharajani, Lucia Campos Carrascosa, Boris Lamp, Andrea Nist, Thorsten Stiewe, Yoav Shaul, Till Adhikary, Mario M Zaiss, Matthias Lauth, Ulrich Steinhoff, Alexander Visekruna,

Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this reprogramming is mediated ... Read more >>

Nat Commun (Nature communications)
[2019, 10(1):760]

Cited: 5 times

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Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.

Oliver H Robak, Markus M Heimesaat, Andrey A Kruglov, Sandra Prepens, Justus Ninnemann, Birgitt Gutbier, Katrin Reppe, Hubertus Hochrein, Mark Suter, Carsten J Kirschning, Veena Marathe, Jan Buer, Mathias W Hornef, Markus Schnare, Pascal Schneider, Martin Witzenrath, Stefan Bereswill, Ulrich Steinhoff, Norbert Suttorp, Leif E Sander, Catherine Chaput, Bastian Opitz,

Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2018, 128(8):3535-3545]

Cited: 10 times

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IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation.

Safa Alnahas, Stefanie Hagner, Hartmann Raifer, Ayse Kilic, Georg Gasteiger, Reinier Mutters, Anne Hellhund, Immo Prinz, Olaf Pinkenburg, Alexander Visekruna, Holger Garn, Ulrich Steinhoff,

Alterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments allergic airway inflammation (AAI) remain unclear. We ... Read more >>

Front Immunol (Frontiers in immunology)
[2017, 8:1562]

Cited: 4 times

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Functional heterogeneity of gut-resident regulatory T cells.

Maik Luu, Ulrich Steinhoff, Alexander Visekruna,

Regulatory T cells (Treg cells) have a central role in the maintenance of intestinal homeostasis by restraining inappropriate immune responses in the healthy gut. Although distinct intestinal immune cell populations have been described to exhibit regulatory activity, several genetic and functional studies provided a strong evidence for a pivotal role ... Read more >>

Clin Transl Immunology (Clinical & translational immunology)
[2017, 6(9):e156]

Cited: 15 times

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Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7.

Niyati Vachharajani, Thorsten Joeris, Maik Luu, Sabrina Hartmann, Sabine Pautz, Elena Jenike, Georgios Pantazis, Immo Prinz, Markus J Hofer, Ulrich Steinhoff, Alexander Visekruna,

Chronic inflammation is a well-known risk factor in development of intestinal tumorigenesis, although the exact mechanisms underlying development of colitis-associated cancer (CAC) still remain obscure. The activity and function of immunoproteasome has been extensively analyzed in the context of inflammation and infectious diseases. Here, we show that the proteasomal immunosubunit ... Read more >>

Oncotarget (Oncotarget)
[2017, :]

Cited: 6 times

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Autoimmune Renal Disease Is Exacerbated by S1P-Receptor-1-Dependent Intestinal Th17 Cell Migration to the Kidney.

Christian F Krebs, Hans-Joachim Paust, Sonja Krohn, Tobias Koyro, Silke R Brix, Jan-Hendrik Riedel, Patricia Bartsch, Thorsten Wiech, Catherine Meyer-Schwesinger, Jiabin Huang, Nicole Fischer, Philipp Busch, Hans-Willi Mittrücker, Ulrich Steinhoff, Brigitta Stockinger, Laura Garcia Perez, Ulrich O Wenzel, Matthias Janneck, Oliver M Steinmetz, Nicola Gagliani, Rolf A K Stahl, Samuel Huber, Jan-Eric Turner, Ulf Panzer,

Th17 cells are most abundant in the gut, where their presence depends on the intestinal microbiota. Here, we examined whether intestinal Th17 cells contribute to extra-intestinal Th17 responses in autoimmune kidney disease. We found high frequencies of Th17 cells in the kidneys of patients with antineutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis. ... Read more >>

Immunity (Immunity)
[2016, 45(5):1078-1092]

Cited: 20 times

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Prevention of colitis-associated cancer by selective targeting of immunoproteasome subunit LMP7.

Niyati Vachharajani, Thorsten Joeris, Maik Luu, Sabrina Hartmann, Sabine Pautz, Elena Jenike, Georgios Pantazis, Immo Prinz, Markus J Hofer, Ulrich Steinhoff, Alexander Visekruna,

Chronic inflammation is a well-known risk factor in development of intestinal tumorigenesis, although the exact mechanisms underlying development of colitis-associated cancer (CAC) still remain obscure. The activity and function of immunoproteasome has been extensively analyzed in the context of inflammation and infectious diseases. Here, we show that the proteasomal immunosubunit ... Read more >>

Oncotarget (Oncotarget)
[2017, 8(31):50447-50459]

Cited: 3 times

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Diagnostic accuracy of rKLO8 versus rK26 ELISAs for screening of canine visceral leishmaniasis.

Lily P Martínez Abad, Caroline S Almeida, Ana Márcia M Mattos, Ana Carolina P Mendonça, Márcio J M Alves, Aimara C Pinheiro, Renato Porrozzi, Elfadil Abass, Ulrich Steinhoff, Henrique C Teixeira,

Canine visceral leishmaniasis (CVL) represents an important public health issue. Despite numerous diagnostic tests available, CVL diagnosis still needs to be improved to achieve a more accurate detection rate. Recently, rKLO8, a new antigenic protein of Sudanese Leishmania donovani, was studied for the first time in diagnosis of human visceral ... Read more >>

Acta Trop. (Acta tropica)
[2017, 166:133-138]

Cited: 2 times

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Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation.

Holger Garn, Sabine Bahn, Bernhard T Baune, Elisabeth B Binder, Hans Bisgaard, Talal A Chatila, Triantafyllos Chavakis, Carsten Culmsee, Udo Dannlowski, Steffen Gay, James Gern, Tari Haahtela, Tilo Kircher, Ulf Müller-Ladner, Markus F Neurath, Klaus T Preissner, Christoph Reinhardt, Graham Rook, Shannon Russell, Bernd Schmeck, Thaddeus Stappenbeck, Ulrich Steinhoff, Jim van Os, Scott Weiss, Michael Zemlin, Harald Renz,

Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; ... Read more >>

J. Allergy Clin. Immunol. (The Journal of allergy and clinical immunology)
[2016, 138(1):47-56]

Cited: 2 times

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Antigen receptor-mediated depletion of FOXP3 in induced regulatory T-lymphocytes via PTPN2 and FOXO1.

Evita Bothur, Hartmann Raifer, Claudia Haftmann, Anna-Barbara Stittrich, Anne Brüstle, Dirk Brenner, Nadine Bollig, Maria Bieringer, Chol-Ho Kang, Katharina Reinhard, Bärbel Camara, Magdalena Huber, Alexander Visekruna, Ulrich Steinhoff, Antje Repenning, Uta-Maria Bauer, Veronika Sexl, Andreas Radbruch, Tim Sparwasser, Mir-Farzin Mashreghi, Tak Wah Mak, Michael Lohoff,

Regulatory T-cells induced via IL-2 and TGFβ in vitro (iTreg) suppress immune cells and are potential therapeutics during autoimmunity. However, several reports described their re-differentiation into pathogenic cells in vivo and loss of their key functional transcription factor (TF) FOXP3 after T-cell antigen receptor (TCR)-signalling in vitro. Here, we show ... Read more >>

Nat Commun (Nature communications)
[2015, 6:8576]

Cited: 11 times

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Heterogeneity of Leishmania donovani parasites complicates diagnosis of visceral leishmaniasis: comparison of different serological tests in three endemic regions.

Elfadil Abass, Cholho Kang, Franjo Martinkovic, Saul J Semião-Santos, Shyam Sundar, Peter Walden, Renaud Piarroux, Abdallah El Harith, Michael Lohoff, Ulrich Steinhoff,

Diagnostic tests for visceral leishmaniasis that are based on antigens of a single Leishmania strain can have low diagnostic performance in regions where heterologous parasites predominate. The aim of this study was to investigate and compare the performance of five serological tests, based on different Leishmania antigens, in three endemic ... Read more >>

PLoS ONE (PloS one)
[2015, 10(3):e0116408]

Cited: 17 times

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Environmentally determined differences in the murine lung microbiota and their relation to alveolar architecture.

Yeojun Yun, Girish Srinivas, Sven Kuenzel, Miriam Linnenbrink, Safa Alnahas, Kenneth D Bruce, Ulrich Steinhoff, John F Baines, Ulrich E Schaible,

Commensal bacteria control the micro-ecology of metazoan epithelial surfaces with pivotal effect on tissue homeostasis and host defense. In contrast to the upper respiratory tract, the lower respiratory tract of healthy individuals has largely been considered free of microorganisms. To understand airway micro-ecology we studied microbiota of sterilely excised lungs ... Read more >>

PLoS ONE (PloS one)
[2014, 9(12):e113466]

Cited: 34 times

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Lack of microbiota reduces innate responses and enhances adaptive immunity against Listeria monocytogenes infection.

Hans-Willi Mittrücker, Daniel Seidel, Paul W Bland, Agnieszka Zarzycka, Stefan H E Kaufmann, Alexander Visekruna, Ulrich Steinhoff,

The intestinal microbiota influences not only metabolic processes, but also the mucosal and systemic immune systems. Here, we compare innate and adaptive immune responses against the intracellular pathogen Listeria monocytogenes in germfree (GF) and conventional mice. We show that animals without endogenous microbiota are highly susceptible to primary infection with ... Read more >>

Eur. J. Immunol. (European journal of immunology)
[2014, 44(6):1710-1715]

Cited: 7 times

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β5i subunit deficiency of the immunoproteasome leads to reduced Th2 response in OVA induced acute asthma.

Anton Volkov, Stefanie Hagner, Stephan Löser, Safa Alnahas, Hartmann Raifer, Anne Hellhund, Holger Garn, Ulrich Steinhoff,

The immunoproteasome subunit β5i has been shown to play an important role in Th1/Th17 driven models of colitis and arthritis. However, the function of β5i in Th2 dependent diseases remains enigmatic. To study the role of β5i in Th2-driven pathology, β5i knockout (KO) and control mice were tested in different ... Read more >>

PLoS ONE (PloS one)
[2013, 8(4):e60565]

Cited: 5 times

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rKLO8, a novel Leishmania donovani - derived recombinant immunodominant protein for sensitive detection of visceral leishmaniasis in Sudan.

Elfadil Abass, Nadine Bollig, Katharina Reinhard, Bärbel Camara, Durria Mansour, Alexander Visekruna, Michael Lohoff, Ulrich Steinhoff,

BACKGROUND: For effective control of visceral leishmaniasis (VL) in East Africa, new rapid diagnostic tests are required to replace current tests with low sensitivity. The aim of this study is to improve diagnosis of VL in East Africa by testing a new antigen from an autochthonous L. donovani strain in ... Read more >>

PLoS Negl Trop Dis (PLoS neglected tropical diseases)
[2013, 7(7):e2322]

Cited: 20 times

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A key role for NF-κB transcription factor c-Rel in T-lymphocyte-differentiation and effector functions.

Alexander Visekruna, Anton Volkov, Ulrich Steinhoff,

The transcription factors of the Rel/NF-κB family function as key regulators of innate and adoptive immunity. Tightly and temporally controlled activation of NF-κB-signalling pathways ensures prevention of harmful immune cell dysregulation, whereas a loss of control leads to pathological conditions such as severe inflammation, autoimmune disease, and inflammation-associated oncogenesis. Five ... Read more >>

Clin. Dev. Immunol. (Clinical & developmental immunology)
[2012, 2012:239368]

Cited: 18 times

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c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection.

Katharina Reinhard, Magdalena Huber, Corinna Wostl, Anne Hellhund, Anne Toboldt, Elfadil Abass, Bärbel Casper, Thorsten Joeris, Christian Herr, Robert Bals, Ulrich Steinhoff, Michael Lohoff, Alexander Visekruna,

Recent studies demonstrated the crucial role of c-Rel in directing Treg lineage commitment and its involvement in T helper 1 (Th1) cell-mediated autoimmune inflammation. We thus wondered whether these opposite functions of c-Rel influence the course of antiparasitic immune responses against Leishmania major, an accepted model for the impact of ... Read more >>

Eur. J. Immunol. (European journal of immunology)
[2011, 41(5):1388-1398]

Cited: 13 times

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c-Rel is crucial for the induction of Foxp3(+) regulatory CD4(+) T cells but not T(H)17 cells.

Alexander Visekruna, Magdalena Huber, Anne Hellhund, Evita Bothur, Katharina Reinhard, Nadine Bollig, Nicole Schmidt, Thorsten Joeris, Michael Lohoff, Ulrich Steinhoff,

The NF-kappaB/Rel family member c-Rel was described to be required for the development of T(H)1 responses. However, the role of c-Rel in the differentiation of T(H)17 and regulatory CD4(+)Foxp3(+) T cells (Treg) remains obscure. Here, we show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory T(H)17 cells ... Read more >>

Eur. J. Immunol. (European journal of immunology)
[2010, 40(3):671-676]

Cited: 54 times

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Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection.

Patricia Neves, Vicky Lampropoulou, Elisabeth Calderon-Gomez, Toralf Roch, Ulrik Stervbo, Ping Shen, Anja A Kühl, Christoph Loddenkemper, Matthias Haury, Sergei A Nedospasov, Stefan H E Kaufmann, Ulrich Steinhoff, Dinis P Calado, Simon Fillatreau,

The myeloid differentiation primary response gene 88 (Myd88) is critical for protection against pathogens. However, we demonstrate here that MyD88 expression in B cells inhibits resistance of mice to Salmonella typhimurium infection. Selective deficiency of Myd88 in B cells improved control of bacterial replication and prolonged survival of the infected ... Read more >>

Immunity (Immunity)
[2010, 33(5):777-790]

Cited: 133 times

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MyD88/TLR9 mediated immunopathology and gut microbiota dynamics in a novel murine model of intestinal graft-versus-host disease.

Markus M Heimesaat, Axel Nogai, Stefan Bereswill, Rita Plickert, André Fischer, Christoph Loddenkemper, Ulrich Steinhoff, Sandrine Tchaptchet, Eckhard Thiel, Marina A Freudenberg, Ulf B Göbel, Lutz Uharek,

BACKGROUND: The bacterial microflora aggravates graft-versus-host-disease (GvHD) after allogeneic stem cell transplantation, but the underlying mechanisms of manifestations of intestinal GvHD (iGvHD) in the gut remain poorly understood. AIM: To analyse the gut flora composition and the impact of bacterial sensing via Toll-like receptors (TLRs) in iGvHD. METHODS: By mimicking ... Read more >>

Gut (Gut)
[2010, 59(8):1079-1087]

Cited: 122 times

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Targeting the proteasome: partial inhibition of the proteasome by bortezomib or deletion of the immunosubunit LMP7 attenuates experimental colitis.

Nicole Schmidt, Erik Gonzalez, Alexander Visekruna, Anja A Kühl, Christoph Loddenkemper, Hans Mollenkopf, Stefan H E Kaufmann, Ulrich Steinhoff, Thorsten Joeris,

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD), comprising Crohn s disease and ulcerative colitis, is characterised by chronic relapsing inflammation of the gut. Increased proteasome activity, associated with the expression of immunoproteasomes, was found to enhance proinflammatory signalling and thus promotes inflammation in patients with IBD. The aim of this ... Read more >>

Gut (Gut)
[2010, 59(7):896-906]

Cited: 80 times

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Association between activation of atypical NF-kappaB1 p105 signaling pathway and nuclear beta-catenin accumulation in colorectal carcinoma.

Johannes C Lauscher, Jörn Gröne, Sonja Dullat, Birgit Hotz, Jörg-P Ritz, Ulrich Steinhoff, Heinz-J Buhr, Alexander Visekruna,

Recent studies have demonstrated that increased expression of coding region determinant-binding protein (CRD-BP) in response to beta-catenin signaling leads to the stabilization of beta-TrCP1, a substrate-specific component of SCF E3 ubiquitin ligase complex, resulting in an accelerated degradation of IkappaBalpha and activation of canonical nuclear factor-kappaB (NF-kappaB) pathway. Here, we ... Read more >>

Mol. Carcinog. (Molecular carcinogenesis)
[2010, 49(2):121-129]

Cited: 3 times

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