Immune privilege of skin stem cells: What do we know and what can we learn?

The skin forms a barrier that prevents dehydration and keeps us safe from pathogens. To ensure proper function, the skin possesses a myriad of stem cell populations that are essential for maintenance and repair upon damage. In order to protect, the skin is also an active immunological site, with abundant resident immune cells and strong recruitment of even more immune cells during wounding or infection. Such active and strong immunity makes the skin susceptible to a diverse spectrum of autoimmune diseases, such as vitiligo and alopecia areata. Conversely, despite constant immune surveillance, the skin is also a tissue where frequent malignancies occur, which suggests that immune evasion must also take place. Skin stem cells play a crucial role during both regeneration and tumorigenesis. How immune cells, and in particular T cells, interact with skin stem cells and the implications this crosstalk has in skin disease (both autoimmunity and cancer) is not fully understood. Uncovering the mechanisms governing immune-stem cells interactions in the skin is critical for the development of new therapeutic strategies to safeguard susceptible cells during autoimmunity and, conversely, to improve cancer immunotherapy. Here, I will discuss how distinct skin stem cell populations are attacked by, or conversely, cloaked from immune cells, and the implications their differences have in autoimmunity and cancer.