Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells
Pedro Lee,
Rupali Gund,
Abhik Dutta,
Neha Pincha,
Isha Rana,
Subhasri Ghosh,
Deborah Witherden,
Eve Kandyba,
Amanda MacLeod,
Krzysztof Kobielak,
Wendy L Havran,
Colin Jamora
Affiliations
Pedro Lee
Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, United States
Rupali Gund
IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India
Abhik Dutta
IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India
Neha Pincha
IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India; Graduate Studies, Manipal University, Manipal, India
Isha Rana
IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India; Shanmugha Arts, Science, Technology and Research Academy (SASTRA) University, Thanjavur, India
Subhasri Ghosh
IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India
Deborah Witherden
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, United States
Eve Kandyba
Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research, Department of Pathology, University of Southern California, Los Angeles, United States
Amanda MacLeod
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, United States
Krzysztof Kobielak
Eli and Edythe Broad Center for Regenerative Medicine & Stem Cell Research, Department of Pathology, University of Southern California, Los Angeles, United States
Wendy L Havran
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, United States
IFOM-inStem Joint Research Laboratory, Centre for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India
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.