Figure 7. Schematic pathway of Ang II–TGF-β interaction in the CNS.

(i) During neuro­inflammation Ang II targets astrocytes and microglia via the AT1R. (ii) Following Ang II stimulation, microglial cells increase production of TGF-β. (iii) Astrocytes in turn mainly increase their TSP-1 secretion, which (iv) cleaves off LAP and activates TGF-β. (v) More active TGF-β in the brain creates a permissive niche in the CNS, allowing T cells to obtain a more inflammatory phenotype, and therefore worsens EAE. (vi) CA inhibits this TGF-β–activating cascade at the beginning. (vii) LSKL blocks the binding between TSP-1 and TGF-β.