Intestinal Immune Regulation

Our main focus is the role of antigen-specific Th cells in human immune responses. T helper (Th) cells are central organizers of immune responses. Via their T cell receptor, they are able to recognize a specific antigen. By releasing different effector cytokines, they can initiate a immune response appropriate to the antigen. However, inappropriate or too strong immune reactions can lead to immune pathologies, such autoimmunity, chronic inflammation or allergies. A specialized Th cell subpopulation, the regulatory T cells (Tregs) on the other hand, have suppressive properties. This enables them to dampen or even prevent the immune response against a certain antigen.

However, which T cells react against a particular antigen, which antigens are at all recognized and how protective immunity and tolerance is maintained or disrupted is in many clinically situations not known. Using novel approaches to analyze antigen-reactive Th cells directly ex vivo from human samples, we are conducting studies to understand why in patients with chronic inflammatory diseases, such as inflammatory bowel disease or allergies, tolerance mechanisms fail. Antigen-reactive Th cell analysis can be combined with powerful state-of-the-art analytical technologies, such as multidimensional flow cytometry, (single cell) transcriptomics, TCR sequencing and proteomics, to provide single cell information at high resolution. We aim to elucidate the interaction between environmental factors and microbial and inflammatory processes that lead to dysfunctions and inflammation. The analysis of these fundamental processes directly in cells from the human immune system will significantly advance our understanding of basic mechanisms underlying human immune-mediated diseases and speed up the development of new diagnostic as well as therapeutic strategies for chronic inflammatory diseases, autoimmunity or allergy.

• Human T cell responses against microbiota
• Antigen-specific T cells in chronic inflammatory diseases
• Molecular regulation of microbiota-reactive T cells
• Induction and functional characterization of human antigen-specific Th17 cell subsets
• Oral tolerance induced by food-specific T cells

1. Focus on fungi

Iliyan D Iliev, Gordon D Brown, Petra Bacher, Sarah L Gaffen, Joseph Heitman, Bruce S Klein, Michail S Lionakis. Focus on fungi. PubMed 2024 Sep 19; PMID: 39303681; PMCID: PMC11722117; DOI: 10.1016/j.cell.2024.08.016

2. Autoantigen-specific CD4⁺ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases

Carina Saggau, Petra Bacher, Daniela Esser, Mahdi Rasa, Silja Meise, Nicola Mohr, Nora Kohlstedt, Andreas Hutloff, Sarah-Sophie Schacht, Justina Dargvainiene, Gabriela Rios Martini, Klarissa H Stürner, Ina Schröder, Robert Markewitz, Johannes Hartl, Maria Hastermann, Ankelien Duchow, Patrick Schindler, Mareike Becker, Carolin Bautista, Judith Gottfreund, Jörn Walter, Julia K Polansky, Mingxing Yang, Reza Naghavian, Mareike Wendorff, Ev-Marie Schuster, Andreas Dahl, Andreas Petzold, Susanne Reinhardt, Andre Franke, Marek Wieczorek, Lea Henschel, Daniel Berger, Guido Heine, Maike Holtsche, Vivien Häußler, Christian Peters, Enno Schmidt, Simon Fillatreau, Dirk H Busch, Klaus-Peter Wandinger, Kilian Schober, Roland Martin, Friedemann Paul, Frank Leypoldt, Alexander Scheffold. Autoantigen-specific CD4⁺ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases. PubMed 2024 Oct 8; PMID: 39226901; DOI: 10.1016/j.immuni.2024.08.005

3. Antigen specificity and cross-reactivity drive functionally diverse anti-Aspergillus fumigatus T cell responses in cystic fibrosis

Carsten Schwarz, Patience Eschenhagen, Henrijette Schmidt, Thordis Hohnstein, Christina Iwert, Claudia Grehn, Jobst Roehmel, Eva Steinke, Mirjam Stahl, Laura Lozza, Ekaterina Tikhonova, Elisa Rosati, Ulrik Stervbo, Nina Babel, Jochen G Mainz, Hilmar Wisplinghoff, Frank Ebel, Lei-Jie Jia, Matthew G Blango, Peter Hortschansky, Sascha Brunke, Bernhard Hube, Axel A Brakhage, Olaf Kniemeyer, Alexander Scheffold, Petra Bacher. PubMed 2023 Mar 1; PMID:  36701198;PMCID:   PMC9974102; DOI: 10.1172/JCI161593

4. Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease

Martini GR, Tikhonova E, Rosati E, DeCelie MB, Sievers LK, Tran F, Lessing M, Bergfeld A, Hinz S, Nikolaus S, Kümpers J, Matysiak A, Hofmann P, Saggau C, Schneiders S, Kamps AK, Jacobs G, Lieb W, Maul J, Siegmund B, Seegers B, Hinrichsen H, Oberg HH, Wesch D, Bereswill S, Heimesaat MM, Rupp J, Kniemeyer O, Brakhage AA, Brunke S, Hube B, Aden K, Franke A, Iliev ID, Scheffold A, Schreiber S, Bacher P. Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T_H1 cell responses in Crohn’s disease. Nat Med. 2023 Oct;29(10):2602-2614. doi: 10.1038/s41591-023-02556-5. Epub 2023 Sep 25. PMID: 37749331; PMCID: PMC10579100.

5. The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

Saggau C, Martini GR, Rosati E, Meise S, Messner B, Kamps AK, Bekel N, Gigla J, Rose R, Voß M, Geisen UM, Reid HM, Sümbül M, Tran F, Berner DK, Khodamoradi Y, Vehreschild MJGT, Cornely O, Koehler P, Krumbholz A, Fickenscher H, Kreuzer O, Schreiber C, Franke A, Schreiber S, Hoyer B, Scheffold A, Bacher P. Immunity. 2022 Aug 12;S1074-7613(22)00396-X.  doi: 10.1016/j.immuni.2022.08.003. Online ahead of print.

6. Low-Avidity CD4+ T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19

Bacher P, Rosati E, Esser D, Rios-Martini G, Saggau C, Schiminsky E, Dargvainiene J, Schöder I, Wieters I, Khodamoradi Y, Eberhardt F, Vehreschild MJGT, Neb H, Sonntagbauer M, Conrad C, Tran F, Rosenstiel P, Markewitz R, Wandinger, K-P, Augustin M, Rybniker J, Kochanek M, Leypoldt F, Cornely OA, Koehler P, Franke A, Scheffold A. Immunity 2020

7. Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans

Bacher P, Hohnstein T, Beerbaum E, Röcker M, Blango MG, Kaufmann S, Röhmel J, Eschenhagen P, Grehn C, Seidel K, Rickerts V, Lozza L, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Ziegler M, Wisplinghoff H, Heine G, Worm M, Siegmund B, Maul J, Creutz P, Tabeling C, Ruwwe-Glösenkamp C, Sander LE, Knosalla C, Brunke S, Hube B, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A. Cell. 2019; 176(6):1340-1355.e15.

8. A novel unconventional T cell population enriched in Crohn’s disease.

Rosati E, Rios Martini G, Pogorelyy MV, Minervina AA, Degenhardt F, Wendorff M, Sari S, Mayr G, Fazio A, Dowds CM, Hauser C, Tran F, von Schönfels W, Pochhammer J, Salnikova MA, Jaeckel C, Gigla JB, Sabet SS, Hübenthal M, Schiminsky E, Schreiber S, Rosenstiel PC, Scheffold A, Thomas PG, Lieb W, Bokemeyer B, Witte M, Aden K, Hendricks A, Schafmayer C, Egberts JH, Mamedov IZ, Bacher P, Franke A. Gut. 2022 Mar 9:gutjnl-2021-325373.

9. Regulatory T Cell Specificity Directs Tolerance versus Allergy against Aeroantigens in Humans

Bacher P, Heinrich F, Stervbo U, Nienen M, Vahldieck M, Iwert C, Vogt K, Kollet J, Babel N, Sawitzki B, Schwarz C, Bereswill S, Heimesaat MM, Heine G, Gadermaier G, Asam C, Assenmacher M, Kniemeyer O, Brakhage AA, Ferreira F, Wallner M, Worm M, Scheffold A. Cell. 2016Nov 3;167(4):1067-1078.e16.

Prof. Dr. rer. nat. Petra Bacher

• PubMed
• ORCiD

• ERC-StG MicroT: Microbiota-T cell interactions – antigen-specificity and regulation in health and disease
• CRU 5010: “Towards a Cure for Adults and Children with Acute Lymphoblastic Leukemia” (CATCH-ALL). Project: The Yin and Yang of anti-cancer CD4+ T cell responses in ALL
• SFB 1526: „Pathomechanisms of Antibody-mediated Autoimmunity (PANTAU) – Insights from Pemphigoid Diseases”. B08: Microbiota-specific T cell responses
• DFG: A pathogen-specific CD4 T cell atlas for chronic inflammatory diseases
• FOR 5042: ”The microbiome as a therapeutic target in inflammatory bowel disease” (miTarget). P1: Early microbiome changes and its antigenic potential in individuals at high-risk for inflammatory bowel diseases
• Cluster of excellence „Precision Medicine in Chronic Inflammation“ (PMI) (EXC 2167-390884018). Integrative Immunogenetics and Cellular Approaches towards Developing an Antigen-Specific Therapy

• Dr. Mario Assenmacher, Marco Vahldieck, Jennifer Pankratz; Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
• Prof. Axel Brakhage, Dr. Olaf Kniemeyer; Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie (HKI), Jena, Germany
• Prof. Oliver Cornely, Angela Steinbach; Klinik I für Innere Medizin, Uniklinik Köln, Köln, Germany
• Prof. Andre Franke, Elisa Rosati; Institut für Klinische Molekularbiologie, CAU Kiel, Germany
• Prof. Dr. Guido Heine, UKSH Campus Kiel, Klinik für Dermatologie, Venerologie und Allergologie
• Prof. Bernhard Hube, Dr. Sascha Brunke; Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie (HKI), Jena, Germany
• Dr. Iliyan Iliev, Associate Professor of Microbiology and Immunology in Medicine; Weill Cornell Medical College, New York, USA
• Dr. Jochen Maul, Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie CBF, Charité – Universitätsmedizin Berlin, Berlin, Germany
• Prof. Alexander Scheffold; Institut für Immunologie, CAU Kiel, Germany
• Dr. Bernd Schnabl, Professor of Medicine; University of California, UC San Diego School of Medicine, San Diego, USA
• Prof. Dr. Christoph Schramm; Universitätsklinikum Hamburg-Eppendorf, Zentrum für Innere Medizin, 1. Med. Klinik und Poliklinik (Gastroenterologie mit Sektionen Infektiologie und Tropenmedizin), Hamburg, Germany
• Prof. Dr. Stefan Schreiber, PD Dr. Konrad Aden; Universitätsklinikum Schleswig-Holstein, Klinik für Innere Medizin I, Institut für Klinische Molekularbiologie (IKMB), Kiel, Germany
• Prof. Dr. Carsten Schwarz, Dr. med. Patience N. Eschenhagen; Klinikum Westbrandenburg, Mukoviszidosezentrum, Potsdam, Germany