Reduction in human epidermal Langerhans cells with age is associated with decline in CXCL14-mediated recruitment of CD14 + monocytes.

Skin provides the first line of physical and immunological defense against the environmental insults. However, the age-related changes in the immune function of the human skin are unclear. Here, we investigated the age-related changes in epidermal Langerhans cells (LCs), which play a sentinel role in the initiation of the immune responses in the skin. We found a significant reduction in the number of epidermal LCs in the sun-protected skin with age. Among the possible explanations for this reduction, we found that the number of CD14 CD207 CCR6 dermal-resident monocytes that can differentiate into epidermal LCs were markedly reduced with age (p = 0.0057). Among the chemokines that can recruit these cells into the skin, the expression of CXCL14 was significantly down-regulated in the epidermal keratinocytes with age. Importantly, we discovered that young skin recruited significantly more monocytic THP-1 cells compared to old skin ex vivo. This recruitment was blocked by CXCL14 neutralizing antibody and was conversely promoted by CXCL14 treatment. Collectively, our findings indicate that decreased CXCL14-mediated recruitment of CD14 monocytes in the human skin results in the reduction of epidermal LCs with age, and CXCL14 may provide a novel therapeutic target for the prevention of age-related LC reduction.