CELLULAR AND MOLECULAR
IMMUNOREGULATION

Revealing the secrets of immunity.

Mgr. Jan Frič, Ph.D.

Research focus
The team focuses on different aspects of the human immune response and on how the underlying me­chanisms of immunity are linked with the development of disorders and pathologies. The main objectives are addressing i) new key events in myeloid cell signaling, describing the role of the Calcineurin–NFAT axis in the control of myeloid cell response to pathogens; (ii) novel important roles of immune response in the progression of human sepsis; (iii) the research in the field of immune senescence, addressing the im­munosenescent phenotype in a number of cohorts of patients with various disorders and in child cancer survivors; iv) the development of 3D models of human mucosal tissues to mimic and study the immu­nocompetence of these complex microenvironments. Our tight collaboration with clinicians creates the opportunity to perform pre-clinical research with a strong translational approach, filling the gap between bench and bedside.

Research objectives

  • Description of the role of pattern recognition receptors in acute immune response, chronic inflammation and tissue regeneration using immune cells and mucosal tissue 3D organoids.
  • Characterization of dynamic changes of the immune system during onset and progression of septic shock.
  • Description of molecular crosstalk between innate immune signaling and metabolic changes in myeloid cells.
  • Describing the mechanisms responsible for the onset of innate immune memory as a tool to reduce the susceptibility of patients to respiratory infections.
  • Develop translational research in the field of immunosenescese and inflammaging through analysis of various cohorts of the elderly, patients with chronic inflammatory disorders and child cancer survivors.

Main partners

  • Department of Pathophysiology, Third Faculty of Medicine, Charles University in Prague, Czech Republic
  • Veterinary Research Institute, Brno
  • Institute of Hematology and Blood Transfusion in Prague
  • Czech Centre for Phenogenomics, Institute of Molecular Genetics, Prague
  • Central European Institute of Technology, Brno
  • University of Perugia, Italy
  • Latvian Institute of Organic Synthesis, Riga

Offered services and expertise

  • FACS sorting of cells using MoFlo.
  • Multiparametric FACS analysis.
  • Histology and imaging techniques.
  • Tailored cell signaling reposter cell lines.
  • Screening of signaling processes using various human primary immunocytes.

Top publications

Lázničková P et al: Childhood survivors of high-risk neuroblastoma show signs of immune recovery and not immunosenescence. Eur J Immunol.2020 Aug 3. doi: 10.1002/eji.202048541.

Hortová-Kohoutková M et al: Phagocytosis-inflammation Crosstalk in Sepsis: New Avenues for Therapeutic Intervention. Shock.2020 Jun 8. doi: 10.1097/SHK.0000000000001541

Bendíčková K et al: Roles of IL-2 in bridging adaptive and innate immunity, and as a tool for cellular immunotherapy. J Leukoc Biol.2020 Jul;108(1):427-437. doi: 10.1002/JLB.5MIR0420-055R.

Jose SS et al: Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment. Clin Transl Immunology.2020 May 5;9(5):e1131. doi: 10.1002/cti2.1131.

Bendíčková K et al: Calcineurin inhibitors reduce NFAT-dependent expression of antifungal pentraxin-3 by human monocytes. J Leukoc Biol.2020 Mar;107(3):497-508. doi: 10.1002/JLB.4VMA0318-138R.

Mencarelli A et al: Calcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis. Nat Commun. 2018 Mar 16;9(1):1102. doi: 10.1038/s41467-018-03495-3.

Bendíčková K et al: Calcineurin-NFAT signalling in myeloid leucocytes: new prospects and pitfalls in immunosuppressive therapy. EMBO Mol Med.2017 Aug;9(8):990-999. doi: 10.15252/emmm.201707698.

Zelante T et al: Impaired calcineurin signaling in myeloid cells results in downregulation of pentraxin-3 and increased susceptibility to aspergillosis. Mucosal Immunol.2017 Mar;10(2):470-480. doi: 10.1038/mi.2016.52.

Other selected results

The CMI has published series of papers (Mucosal Immunology, Cell Reports, Stem Cells, EMBO Molecular Medicine and Blood) showing new important mechanism of immune protection against pathogens and myeloid cells development

The CMI has shown that immunosuppressive drugs (such as Cyclosporine A or Tacrolimus) affect function of calcineurin NFAT signaling pathway in myeloid cells and their precursors, which causes dysregulation of myelopoiesis and increased susceptibility to infections. These results are important for understanding the complications of immunosuppressive therapies.