SFB 1054 Seminar - Dietmar Zaiss
Institute of Immunology and Infection Research, University of Edinburgh, UK
21.06.2018 at 12:15
Title: How CD4 T-cells sense and adapt to changes in local inflammation
Fending off infections while at the same time maintaining tissue homeostasis under inflammatory conditions is a central challenge for the immune system. The underlying mechanisms by which pro- and anti-inflammatory stimuli are balanced to ensure efficient pathogen clearance but also tissue integrity remain largely unresolved.
CD4 T-cells are well-established regulators of local inflammation. We recently discovered that an evolutionary conserved signal transduction pathway, the Epidermal Growth Factor Receptor (EGFR), and two of its ligands, HB-EGF and Amphiregulin, have been adopted by the immune system. Activated CD4 T-cells use the expression of the EGFR and of these two, antagonistic EGFR ligands to regulate local inflammation as well as their own functionality.
To this end, CD4 T-cells employ two fundamentally different mechanisms:
- by forming hetero-complexes with other cytokine receptors, EGFR expression allows CD4 T-cells to respond to inflammatory cytokines in an antigen-independent way and to secrete effector cytokines at the site of inflammation.
- EGFR mediated signals regulate the local release and the responsiveness of CD4 T-cells to TGFβ, a key regulator of local inflammation. Importantly, we found that the high affinity EGFR ligand HB-EGF, blocks TGFβ-mediated Th-17 differentiation of naïve CD4 T-cells.
Based on these two mechanisms our Lab explores how EGFR expression by CD4 effector T-cells allows for the orchestration of efficient immune responses during the different phases of an immune response.
Venue:
BioMedical Center (BMC), Room N 01.017,
Großhaderner Str. 9, Planegg-Martinsried
Host: Dietmar Zehn (B14)
