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 BG, Swirski FK, Weber GF
  (See online at https://doi.org/10.1007/s00281-017-0639-8)
• Fra-2 regulates B cell development by enhancing IRF4 and Foxo1 transcription. J Exp Med. 2017 Jul 3;214(7):2059-2071
  Ubieta K, Garcia M, Grötsch B, Uebe S, Weber GF, Stein M, Ekici A, Schett G, Mielenz D, Bozec A
  (See online at https://doi.org/10.1084/jem.20160514)
• Tumor location determines tissue-specific recruitment of tumor-associated macrophages and antibody-dependent immunotherapy response. Sci Immunol. 2017 Jan 6;2(7)
  Lehmann B, Biburger M, Brückner C, Ipsen-Escobedo A, Gordan S, Lehmann C, Voehringer D, Winkler T, Schaft N, Dudziak D, Sirbu H, Weber GF, Nimmerjahn F
  (See online at https://doi.org/10.1126/sciimmunol.aah6413)
• BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graftversus-host disease. J Clin Invest. 2018 Mar 1;128(3):916-930
  Ullrich E, Abendroth B, Rothamer J, Huber C, Büttner-Herold M, Buchele V, Vogler T, Longerich T, Zundler S, Völkl S, Beilhack A, Rose-John S, Wirtz S, Weber GF, Ghimire S, Kreutz M, Holler E, Mackensen A, Neurath MF, Hildner K
  (See online at https://doi.org/10.1172/JCI89242)
• Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. ACS Nano. 2018 Apr 24;12(4):3378-3384
  Min J, Nothing M, Coble B, Zheng H, Park J, Im H, Weber GF, Castro CM, Swirski FK, Weissleder R, Lee H
  (See online at https://doi.org/10.1021/acsnano.7b08965)
• 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 C, Maier SL, Brunner M, Langheinrich M, Giamarellos-Bourboulis EJ, Gogos C, Armaganidis A, Kunath F, Grützmann R, Weber GF
  (See online at https://doi.org/10.1016/j.jcrc.2018.01.013)
• Gata6(+) Pericardial Cavity Macrophages Relocate to the Injured Heart and Prevent Cardiac Fibrosis. Immunity. 2019 Jul 16;51(1):131-140.e5
  Deniset JF, Belke D, Lee WY, Jorch SK, Deppermann C, Hassanabad AF, Turnbull JD, Teng G, Rozich I, Hudspeth K, Kanno Y, Brooks SR, Hadjantonakis AK, O’Shea JJ, Weber GF, Fedak PWM, Kubes P
  (See online at https://doi.org/10.1016/j.immuni.2019.06.010)
• 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 VE, Ercoli G, Bénard A, Brandl C, Fahnenstiel H, Müller-Winkler J, Weber GF, Denny P, Nitschke L, Andrew PW
  (See online at https://doi.org/10.1371/journal.ppat.1008464)