Role of Interleukin-3 during inflammatory bowel diseases

• Applicant: Alan Bénard, Ph.D.
• Subject Area: General and Visceral Surgery ; Immunology
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424983853

• Final Report Year: 2021

Final Report Abstract

Our data identified interleukin-3 as an important protective mediator during colitis. Mechanistically, we observed that the production of interleukin-3 by mesenchemal stem cells promoted the early recruitment of splenic emergency neutrophils into the colon via CCL5+ T cells. However, we did not yet identify the CD123+ cells involved in this process. We also showed that interleukin-3 drove extramedullary haematopoiesis in spleen thereby sustaining neutrophil mobilization. Our data suggest that the protective effect of IL-3 during colitis is not restricted to splenic neutrophil recruitment but involves other mechanisms. Further investigations are therefore necessary to fully understand the role of IL-3 during colitis.

Publications

• (2019). Influence of Body Mass Index on Long-Term Outcome in Patients with Rectal Cancer-A Single Centre Experience. Cancers (Basel). 2019 Apr 30;11
  Kalb M, Langheinrich MC, Merkel S, Krautz C, Brunner M, Bénard A, Weber K, Pilarsky C, Grützmann R, Weber GF
  (See online at https://doi.org/10.3390/cancers11050609)
• (2020). The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection. PLoS Pathog. 2020 Apr 23;16
  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)
• (2020). Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma. Int J Mol Sci. 2020 Mar 5;21
  Brunner M, Maier K, Rümmele P, Jacobsen A, Merkel S, Bénard A, Krautz C, Kersting S, Grützmann R, Weber GF
  (See online at https://doi.org/10.3390/ijms21051779)
• (2021) Colorectal cancer in Crohn's colitis is associated with advanced tumor invasion and a poorer survival compared with ulcerative colitis: a retrospective dual-center study. Int J Colorectal Dis. 2021 Jan;36(1):141-150
  Vetter LE, Merkel S, Bénard A, Krautz C, Brunner M, Mittelstädt A, Schlegel N, Wiegering A, Germer CT, Weber K, Grützmann R, Weber GF
  (See online at https://doi.org/10.1007/s00384-020-03726-4)
• (2021) Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections. Nat Commun. 2021 Feb 18;12(1):1112
  Bénard A, Jacobsen A, Brunner M, Krautz C, Klösch B, Swierzy I, Naschberger E, Podolska MJ, Kouhestani D, David P, Birkholz T, Castellanos I, Trufa D, Sirbu H, Vetter M, Kremer AE, Hildner K, Hecker A, Edinger F, Tenbusch M, Mühl-Zürbes P, Steinkasserer A, Richter E, Streeck H, Berger MM, Brenner T, Weigand MA, Swirski FK, Schett G, Grützmann R, Weber GF
  (See online at https://doi.org/10.1038/s41467-021-21310-4)