CCL21 contributes to Th17 cell migration in neuroinflammation in obese mice following lead exposure

Obesity and lead exposure can independently cause neuroinflammation, which is associated with neurodegenerative diseases. Although Th17 cells play critical roles in inflammatory diseases of the central nervous system, few studies have evaluated their role in neuroinflammation in the background of obesity and lead exposure. In this study, the mechanism underlying inflammatory injury was evaluated in a mouse model of high fat diet-induced obesity following lead exposure. Neuroinflammation was aggravated in mice with obesity following lead exposure, and this was accompanied by increases in Th17 cells in the brain and IL-17A and IL-22 secretion. An antibody array using Z310, a choroid plexus epithelium cell line, revealed that CCL21 was the most highly altered chemokine. CCL21 expression was higher in the choroid plexus of obese mice treated with lead than in mice with obesity or lead treatment alone and was higher in Z310 cells treated with lead and palmitic acid. CCL21 knockout reduced chemotaxis. Our findings suggest that lead exposure can aggravate inflammation in brain tissues of obese mice, possibly by the CCL21-mediated regulation of the passage of Th17 cells through the blood-cerebrospinal fluid barrier. Our findings provide new insights into the mechanism underlying the combined effects of lead and obesity.