On the left, the presence of Th1 and Th17 cells upregulates (thick lines) the production and release of free radicals from microglia, including NO, superoxide (O₂^–), and hydrogen peroxide (H₂O₂) as well as proinflammatory cytokines such as TNF-α and IL-1β, and downregulates (thin lines) the release of neurotrophic factors such as IGF-1. The result is enhanced neuronal injury, which may trigger the release of increased levels of nitrated/oxidized α-Syn and enhance microglia-mediated neurotoxicity. Tregs can suppress the proinflammatory effects of Th17 cells. On the right, Th2 cells release IL-4, upregulating the release from microglia of neuroprotective IGF-1, downregulating release of free radicals, and resulting in enhanced neuronal protection.