Nannan Liang, Junqin Li, Kaiming Zhang
The skin, as a complex organ, relies on precise and dynamic interactions between the epidermis and dermis to maintain homeostasis and repair damage. The bidirectional communication between mesenchymal stem cells (MSCs) residing in the dermis and keratinocytes (KCs), the principal cells of the epidermis, serves as a central hub driving this process. This review systematically elaborates on the molecular mechanisms and physiopathological significance of the interactions between MSCs and KCs. Mesenchymal stem cells (MSCs) and keratinocytes (KCs) represent the core cell populations that maintain skin physiological homeostasis, regulate wound repair and participate in the pathogenesis of inflammatory skin diseases, and they exhibit a close bidirectional regulatory relationship. On one hand, MSCs can precisely regulate the proliferation, migration, differentiation, inflammation and metabolism of KCs. On the other hand, KCs can secrete chemokines and growth factors such as CXCL2 and IL-6 to recruit MSCs in a targeted manner to the sites of injury or inflammation, activate their differentiation potential and immunomodulatory function. Together, they form a regulatory loop of "KCs recruitment - MSCs activation - reverse regulation of KCs", which jointly participates in the maintenance of skin homeostasis, wound repair and the regulation of disease progression.