In conclusion, our study demonstrated for the first time that in a mouse model of DE, Th22 cells secrete IL-22 after passing through the BBB into the hippocampus and promote the transformation of homeostatic microglia into reactive microglia, which induces an inflammatory response, exacerbates learning and memory impairment and cognitive deficits, and contributes to and accelerates the development of DE. Here, IL22 is linked to Cognitive impairment.