Role of CD99 in regulating homeostasis and differentiation in normal human epidermal keratinocytes

CD99 is a glycoprotein primarily expressed in immune cells. Physiologically, it is involved in the adhesion, migration, and development of immune cells. The presence of CD99 in the skin was first reported in 2016 and its function is yet to be determined. In this study, we aimed to understand the role of CD99 in the skin using normal human epidermal keratinocytes (NHEK). CD99 expression increased with the confluency of NHEK, while the CD99-high expressing NHEK lost their stem cell properties and played a role in barrier function. We characterized CD99-expressing NHEK as cells committed to early differentiation because they expressed early differentiation markers. However, the deficiency of CD99 in NHEK disrupted homeostasis and caused aberrant differentiation, as evidenced by larger cells with lesser Ki67 staining and higher expression of terminal differentiation markers. Hence, we propose that CD99 is involved in maintaining homeostasis and initiating early differentiation in the skin.