Figure 3.

TNFSF receptor–ligand interaction in the CNS parenchyma during neuroinflammation. TNFSF receptors and ligands are expressed on both CNS infiltrating effector immune cells and CNS-resident cells. The interaction of this receptor–ligand greatly influences the outcome of neuroinflammatory disease like multiple sclerosis and EAE. (I) Both neurons and oligodendrocytes express functional DR5 in the CNS during EAE. DR5 on the neurons as well as on oligodendrocytes interacts with TRAIL molecules present on either microglial cells or infiltrating immune cells, leading to apoptosis of DR5-expressing cells. (II) Activated astrocytes and microglial cells up-regulate FasL expression on their surface. The interaction of FasL with Fas-expressing cells leads to apoptosis and elimination of pathogenic effector immune cells. (III) Neuronal cells express TNF and that can interact with TNFR-1 present on various CNS-resident cells, such as astrocytes, microglial cells, and oligodendrocytes. Interactions of TNF with TNFR-1-expressing cells lead to apoptosis of TNFR-1⁺ cells. (IV) Mast cells are known to localize close to the astrocytes during EAE in the brain. CD40L present on mast cells interact with CD40-expressing astrocytes, which induces increased production of inflammatory cytokines and chemokines. Local production of inflammatory molecules can augment inflammation and tissue damage in the CNS.