Impact of the active Nlrp3 inflammasome on signalling in regulatory T cells shaping the tumour microenvironment

Impact of the active Nlrp3 inflammasome on signalling in regulatory T cells shaping the tumour microenvironment

PD Dr. Robert Zeiser (Innere Medizin I, University Medical Center Freiburg)

IL-1β was found in different human cancer tissues and the expression levels of the cytokine are associated with the likelihood to develop distant metastatic spread. The production of bioactive IL-1β is regulated by the Nlrp3 inflammasome which is active in multiple tumour types. The impact of IL-1β on tumour infiltrating CD4⁺FoxP3⁺ regulatory T cells (Tregs) is unclear. In the proposed project I will analyze the signalling pathways in Treg when IL-1β production is impaired due to genetic defects in the Nlrp3 inflammasome components Asc and Nlrp3 by using Asc^-/- and Nlrp3^-/- mice. The planned analysis of the kinases involved in cancer progression will help to clarify if those are also found in activated Treg which may provide a link between tumour cell signalling and immune evasion in the tumour microenvironment.

Abbildung 1: A. Zell Sorter basierte Isolation von murinen CD4⁺CD25^high Treg Zellen die zu 96% Foxp3⁺ sind. B. Immunfluoreszenzmikroskopische Darstellung von Treg Zellen Links: mesenterialer Lymphknoten, x 200, CD4 (grün), Foxp3 (rot), DAPI (blau). Rechts: inguinaler Lymphknoten, x1000, CD4 (grün), Foxp3 (rot), H-2kq (hellblau bei Überlagerung mit CD4 (grün)), DAPI (blau).