Interleukin-3 producing IRA B cells as mediators of acute and delayed immune responses during inflammation

• Applicant: Professor Dr. Georg Weber
• Subject Area: General and Visceral Surgery
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 316129653

• Final Report Year: 2020

Final Report Abstract

Interleukin-3 has been identified as an important mediator during primary and secondary viral pneumonia and as a predictive marker during SARS-CoV-2 infections. Mechanistically, interleukin-3 led to the production of CXCL12 by CD123+ pulmonary epithelial cells leading to the recruitment of type 1 interferon producing circulating plasmacytoid dendritic cells. We identified the generation of interleukin-3 producing IRA B cells during other inflammatory condictions such as inflammatory bowl disease and pancreatitis which is currently investigated further. As well, interleukin-3 seems to play an important role during the development of malignant diseases such as colitis associated colorectal cancer and pancreatic adenocarcinoma.

Publications

• Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol. 2017 Jul;39(5):517-528
  Chousterman, Benjamin G.; Swirski, Filip K. & Weber, Georg F.
  
• Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription. J Exp Med. 2017 Jul 3;214(7):2059-2071
  Ubieta, Kenia; Garcia, Mireia; Grötsch, Bettina; Uebe, Steffen; Weber, Georg F.; Stein, Merle; Ekici, Arif; Schett, Georg; Mielenz, Dirk & Bozec, Aline
  
• Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response. Sci Immunol. 2017 Jan 6;2(7)
  Lehmann, Birgit; Biburger, Markus; Brückner, Christin; Ipsen-Escobedo, Andrea; Gordan, Sina; Lehmann, Christian; Voehringer, David; Winkler, Thomas; Schaft, Niels; Dudziak, Diana; Sirbu, Horia; Weber, Georg F. & Nimmerjahn, Falk
  
• BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graftversus-host disease. J Clin Invest. 2018 Mar 1;128(3):916-930
  Ullrich, Evelyn; Abendroth, Benjamin; Rothamer, Johanna; Huber, Carina; Büttner-Herold, Maike; Buchele, Vera; Vogler, Tina; Longerich, Thomas; Zundler, Sebastian; Völkl, Simon; Beilhack, Andreas; Rose-John, Stefan; Wirtz, Stefan; Weber, Georg F.; Ghimire, Sakhila; Kreutz, Marina; Holler, Ernst; Mackensen, Andreas; Neurath, Markus F.; ... & Hildner, Kai
  
• Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. ACS Nano. 2018 Apr 24;12(4):3378-3384
  Min, Jouha; Nothing, Maria; Coble, Ben; Zheng, Hui; Park, Jongmin; Im, Hyungsoon; Weber, Georg F.; Castro, Cesar M.; Swirski, Filip K.; Weissleder, Ralph & Lee, Hakho
  
• Reduced circulating B cells and plasma IgM levels are associated with decreased survival in sepsis - A meta-analysis. J Crit Care. 2018 Jun;45:71-75
  Krautz, Christian; Maier, Sarah L.; Brunner, Maximilian; Langheinrich, Melanie; Giamarellos-Bourboulis, Evangelos J.; Gogos, Charalambos; Armaganidis, Apostolos; Kunath, Frank; Grützmann, Robert & Weber, Georg F.
  
• Gata6(+) Pericardial Cavity Macrophages Relocate to the Injured Heart and Prevent Cardiac Fibrosis. Immunity. 2019 Jul 16;51(1):131-140.e5
  Deniset, Justin F.; Belke, Darrell; Lee, Woo-Yong; Jorch, Selina K.; Deppermann, Carsten; Hassanabad, Ali Fatehi; Turnbull, Jeannine D.; Teng, Guoqi; Rozich, Isaiah; Hudspeth, Kelly; Kanno, Yuka; Brooks, Stephen R.; Hadjantonakis, Anna-Katerina; O’Shea, John J.; Weber, Georg F.; Fedak, Paul W.M. & Kubes, Paul
  
• The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection. PLoS Pathog. 2020 Apr 23;16(4):e1008464
  Fernandes, Vitor E.; Ercoli, Giuseppe; Bénard, Alan; Brandl, Carolin; Fahnenstiel, Hannah; Müller-Winkler, Jennifer; Weber, Georg F.; Denny, Paul; Nitschke, Lars & Andrew, Peter W.