Systemmedizinischer Ansatz zur Analyses des Immunrepertoires bei chronisch-entzündlichen Darmerkrankungen (CED)

• Antragsteller: Professor Dr. Andre Franke
• Fachliche Zuordnung: Gastroenterologie ; Humangenetik
• Förderung: Förderung von 2019 bis 2021
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 409661003

• Erstellungsjahr: 2022

Zusammenfassung der Projektergebnisse

In this study, we collected peripheral blood and intestinal tissue from 23 IBD and CRC patients. 16 data layers were produced for the analysis of peripheral and intestinal immune repertoire, the intestinal microbiome and HLA genetics. A family of TCRs was identified to be selectively enriched in CD patients. The identified TCRs were present in all the analysed T cell subpopulations (naïve and memory CD4+ and CD8+ T cells), however they were particularly abundant in the CD8+ fraction and secondarily in the memory CD4+ fraction. These findings lead to further analyses of these TCR family. A meta-analysis integrating the different data layers is currently ongoing aiming at (i) the identification of additional features correlating with the identified Crohn-associated T cells; (ii) the identification of associations between immune repertoire and microbiome or/and genetic features in IBD as compared to CRC; (iii) imputation of TCR-HLA specificity and analysis of presence and abundance of TCRs reactive to known risk and protective HLA alleles for IBD.

Projektbezogene Publikationen (Auswahl)

• Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19. Immunity, 53(6), 1296-1314.e9.
  Bernardes, Joana P.; Mishra, Neha; Tran, Florian; Bahmer, Thomas; Best, Lena; Blase, Johanna I.; Bordoni, Dora; Franzenburg, Jeanette; Geisen, Ulf; Josephs-Spaulding, Jonathan; Köhler, Philipp; Künstner, Axel; Rosati, Elisa; Aschenbrenner, Anna C.; Bacher, Petra; Baran, Nathan; Boysen, Teide; Brandt, Burkhard; Bruse, Niklas ... & Ziebuhr, John
  
• Low-Avidity CD4+ T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19. Immunity, 53(6), 1258-1271.e5.
  Bacher, Petra; Rosati, Elisa; Esser, Daniela; Martini, Gabriela Rios; Saggau, Carina; Schiminsky, Esther; Dargvainiene, Justina; Schröder, Ina; Wieters, Imke; Khodamoradi, Yascha; Eberhardt, Fabian; Vehreschild, Maria J.G.T.; Neb, Holger; Sonntagbauer, Michael; Conrad, Claudio; Tran, Florian; Rosenstiel, Philip; Markewitz, Robert; Wandinger, Klaus-Peter ... & Scheffold, Alexander
  
• Primary and secondary anti-viral response captured by the dynamics and phenotype of individual T cell clones. eLife, 9.
  Minervina, Anastasia A.; Pogorelyy, Mikhail V.; Komech, Ekaterina A.; Karnaukhov, Vadim K.; Bacher, Petra; Rosati, Elisa; Franke, Andre; Chudakov, Dmitriy M.; Mamedov, Ilgar Z.; Lebedev, Yuri B.; Mora, Thierry & Walczak, Aleksandra M.
  
• ”Analysis of the peripheral T-cell receptor repertoire (TCR) identifies inflammatory bowel disease (IBD) specific features“. Conference abstract and poster presentation: International Cluster Symposium "Precision Medicine in Chronic Inflammation'", February 17-18, 2020, Kiel, Germany
  Elisa Rosati, Antonella Fazio, Mikhail V. Pogorelyy, Anastasia A. Minervina, Ilgar Mamedov, Matthias Huebenthal, Frauke Degenhardt, Mareike Wendorff, Petra Bacher, Wolfgang Lieb, Stefan Schreiber, Berndt Bokemeyer, Petra Bacher & Andre Franke
  
• ”Unveiling diseaseassociated markers in the peripheral T-cell receptor repertoire of Crohn’s disease patients”. Conference abstract and poster presentation: Next Gen Immunology 2020 (NGI2020), February 2-5, 2020, Weizmann Institute of Science, Israel
  Elisa Rosati, Antonella Fazio, Mikhail V. Pogorelyy, Anastasia A. Minervina, Ilgar Mamedov, Matthias Huebenthal, Frauke Degenhardt, Mareike Wendorff, Petra Bacher, Wolfgang Lieb, Stefan Schreiber, Berndt Bokemeyer, Petra Bacher & Andre Franke
  
• A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection. Cells, 10(11), 3234.
  Monaghan, Tanya M.; Duggal, Niharika A.; Rosati, Elisa; Griffin, Ruth; Hughes, Jamie; Roach, Brandi; Yang, David Y.; Wang, Christopher; Wong, Karen; Saxinger, Lynora; Pučić-Baković, Maja; Vučković, Frano; Klicek, Filip; Lauc, Gordan; Tighe, Paddy; Mullish, Benjamin H.; Blanco, Jesus Miguens; McDonald, Julie A. K.; Marchesi, Julian R. ... & Kao, Dina H.
  
• Clonal expansion and activation of tissue-resident memory-like T H 17 cells expressing GM-CSF in the lungs of patients with severe COVID-19. Science Immunology, 6(56).
  Zhao, Yu; Kilian, Christoph; Turner, Jan-Eric; Bosurgi, Lidia; Roedl, Kevin; Bartsch, Patricia; Gnirck, Ann-Christin; Cortesi, Filippo; Schultheiß, Christoph; Hellmig, Malte; Enk, Leon U.B.; Hausmann, Fabian; Borchers, Alina; Wong, Milagros N.; Paust, Hans-Joachim; Siracusa, Francesco; Scheibel, Nicola; Herrmann, Marissa; Rosati, Elisa ... & Krebs, Christian F.
  
• Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T-cell memory formation after mild COVID-19 infection. eLife, 10.
  Minervina, Anastasia A.; Komech, Ekaterina A.; Titov, Aleksei; Bensouda, Koraichi Meriem; Rosati, Elisa; Mamedov, Ilgar Z.; Franke, Andre; Efimov, Grigory A.; Chudakov, Dmitriy M.; Mora, Thierry; Walczak, Aleksandra M.; Lebedev, Yuri B. & Pogorelyy, Mikhail V.
  
• Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations. Human Molecular Genetics, 30(5), 356-369.
  Degenhardt, Frauke; Mayr, Gabriele; Wendorff, Mareike; Boucher, Gabrielle; Ellinghaus, Eva; Ellinghaus, David; ElAbd, Hesham; Rosati, Elisa; Hübenthal, Matthias; Juzenas, Simonas; Abedian, Shifteh; Vahedi, Homayon; Thelma, B. K.; Yang, Suk-Kyun; Ye, Byong Duk; Cheon, Jae Hee; Datta, Lisa Wu; Daryani, Naser Ebrahim; Ellul, Pierre ... & Franke, Andre
  
• “Proteins and T-cells involved in chronic inflammatory diseases (4T-Crohn: Family of T lymphocytes defined by T-cell receptor alpha chains as a clinical Target for Therapeutics and diagnostics in Crohn’s disease).” Application number EP21217058.3. Pending 2021.
  E. Rosati, A. Franke, P. Bacher & I.Z. Mamedov
  
• Resolving SARS-CoV-2 CD4+ T cell specificity via reverse epitope discovery. Cell Reports Medicine, 3(8), 100697.
  Pogorelyy, Mikhail V.; Rosati, Elisa; Minervina, Anastasia A.; Mettelman, Robert C.; Scheffold, Alexander; Franke, Andre; Bacher, Petra & Thomas, Paul G.