CD4 and Autoimmunity: Interleukin (IL)-17-producing CD4+ T cells (T helper [Th]17 cells) orchestrate protective immune responses against bacterial pathogens.1–5 However, dysregulated Th17 activity also contributes significantly to the pathogenesis of various autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, and psoriasis.6–11 Thus, there is an urgent clinical need for therapies that can effectively control Th17-mediated autoimmunity.12,13 However, treatments that are aimed at mitigating Th17-mediated autoimmunity can also impair Th17-dependent anti-bacterial immune responses.