Séminaire CIRI : Dr. Patrick LEGEMBRE

Dr. Patrick LEGEMBRE (Faculté de Pharmacie, U1262 INSERM, 2 rue Docteur Marcland 87025 Limoges – France), " Role of soluble CD95L in the pathology progression of auto-immune disorders such as lupus and ANCA vasculitis "

Abstract: CD95L (also known as FasL or CD178) belongs to the Tumor necrosis factor (TNF) superfamily. This transmembrane ligand can be cleaved by metalloproteases to release a soluble CD95L designated s-CD95L. While the interaction of the membrane-bound CD95L (m-CD95L) to its receptor CD95 (Fas) induces an apoptotic signal leading to cell death, s-CD95L fails to do it and triggers non-apoptotic signaling pathways (e.g., PI3K, NFkB).

We observed that s-CD95L is increased in lupus and ANCA vasculitis patients and this cytokine promotes inflammation using different mechanisms and targeting different immune cells. From these observations, different drugs were designed to selectively prevent the non-apoptotic signal without affecting the apoptotic one, which is essential to eliminate infected and transformed cells. The pro-inflammatory mechanism induced by s-CD95L accumulation will be discuss in this presentation.