MAPK8 and Alzheimer disease: In addition to the preceding disorders that decrease IL-17 (and selectively IL-22) production, the distinctive feature of CMC and the principal of physiologic homogeneity led to the discovery of IEI that cause impaired responses to IL-17 due to either autosomal dominant (AD) mutations in the IL-17F cytokine [54], AR mutations in the IL-17 receptor subunits (IL17RA or IL17RC) [54,55,56,57,58], AR mutations in the adaptor molecule required for IL-17 receptor signaling (ACT1) [59,60,61,62,63], or AD mutations in the kinase essential for its signaling (JNK1) [64].