We are investigating the role of T-helper (Th) cells in immune-mediated diseases. Using novel approaches for the direct analysis of antigen-reactive Th cells, we try to understand why tolerance mechanisms of the immune system fail in patients with chronic inflammatory diseases.
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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.
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.
2. 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
3. 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.
4. 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.
5. T cell immunity to commensal fungi.
Scheffold A, Bacher P, LeibundGut-Landmann S. Curr Opin Microbiol. 2020 Dec;58:116-123.
6. 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. 2016 Nov 3;167(4):1067-1078.e16.
University Hospital Schleswig-Holstein
Institute of Immunology
Arnold-Heller-Straße 3
Haus U30
24105 Kiel