Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells

  • Lee P
  • Gund R
  • Dutta A
  • et al.
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Abstract

The cutaneous wound-healing program is a product of a complex interplay among diverse cell types within the skin. One fundamental process that is mediated by these reciprocal interactions is the mobilization of local stem cell pools to promote tissue regeneration and repair. Using the ablation of epidermal caspase-8 as a model of wound healing in Mus musculus, we analyzed the signaling components responsible for epithelial stem cell proliferation. We found that IL-1α and IL-7 secreted from keratinocytes work in tandem to expand the activated population of resident epidermal γδT-cells. A downstream effect of activated γδT-cells is the preferential proliferation of hair follicle stem cells. By contrast, IL-1α-dependent stimulation of dermal fibroblasts optimally stimulates epidermal stem cell proliferation. These findings provide new mechanistic insights into the regulation and function of epidermal cell–immune cell interactions and into how components that are classically associated with inflammation can differentially influence distinct stem cell niches within a tissue.The skin is a physical barrier that protects the body from the outside world. If the skin is injured, the body mounts a “wound healing” response to rapidly mend and restore this protective barrier. Wound healing is a complex process and relies on the different types of cells in the skin communicating with each other.Stem cells provide tissues, like the skin, with new cells. Normally, stem cells are in a resting or inactive state. Yet, during wound healing, stem cells near the injured area are awakened and start producing more cells to repair the wound. Understanding how stem cells become activated in a wound has proved challenging because only a small number of cells near a damaged site will respond, and it is difficult to distinguish their response from that of other cells slightly further away.Now, Lee et al. overcome this hurdle by analyzing a genetically engineered mouse in which the entire skin displays a wound healing response, even without any injury or trauma. In these mice, most of the stem cells in the skin are awakened from their normal resting state and behave as if there is a wound to heal.It turns out that a protein called interleukin-1, which is released from damaged skin cells known as keratinocytes, can activate two different groups of stem cells in the skin to help repair the injured tissue. One group lives in the hair follicle and is normally responsible for replacing the hair that falls from the body. Lee et al. found that when the skin is wounded interleukin-1 activates certain immune cells (called γδT-cells). These immune cells then awaken the resting stem cells in the hair follicle to multiply and travel to the wound site to repair the injury. The other group of stem cells resides in the outermost layer of the skin. Interleukin-1 can also activate so-called fibroblast cells, which then stimulate this second group of stem cells to divide and cover the open wound.Quickly healing wounds has many health benefits such as preventing infection and shortening the time to recover from an injury. These new findings may help to repair injured skin in diseases such as diabetes, where wounds can take months to heal and often leads to permanent tissue damage. The next challenge is to identify the cues that instruct the stem cells to travel to the wound site and turn into the specific cells that are required to replace the damaged cells.

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Lee, P., Gund, R., Dutta, A., Pincha, N., Rana, I., Ghosh, S., … Jamora, C. (2017). Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells. ELife, 6. https://doi.org/10.7554/elife.28875

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