Results
Skin Tregs generated early in life arecrucial for adult skin homeostasis
Inchul Cho1,2, Jessie Xu1,2, Niwa Ali1,21. Centre for Stem Cells and Regenerative Medicine, UK; 2. The Francis Crick Institute, UK
References1. Ali, N., Zirak, B., Rodriguez, R., Pauli, M., Truong, H., Lai, K., Ahn, R., Corbin, K., Lowe, M., Scharschmidt, T., Taravati, K., Tan, M., Ricardo-Gonzalez, R., Nosbaum, A., Bertolini, M., Liao,
W., Nestle, F., Paus, R., Cotsarelis, G., Abbas, A. and Rosenblum, M., 2017. Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. Cell, 169(6), pp.1119-1129.e11.2. Mathur, A., Zirak, B., Boothby, I., Tan, M., Cohen, J., Mauro, T., Mehta, P., Lowe, M., Abbas, A., Ali, N. and Rosenblum, M., 2019. Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis
Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair. Immunity, 50(3), pp.655-667.e4.
IntroductionRegulatory T cells (Tregs) govern hair growth and woundhealing by controlling the activity of stem cells in the mouseskin1,2. However, their functions in the neonatal skin duringpostnatal development is unknown.
MethodsWe use Foxp3-EGFP-DTR transgenic mice to deplete Tregsduring early stages of postnatal skin development. The skinfrom Treg-depleted mice are profiled by flow cytometricprofiling, histology and whole skin RNA-sequencing
1. Neonatal Tregs are required for adult skinhomeostasis
Conclusion
2. RNA-seq analysis suggests neuronal defect inthe skin immediately after Treg depletion
3. Tregs are required during early phase ofpostnatal skin development
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DGE Analysis GO Analysis
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Phenotype PBS Late DT Early DT Full DTLack of pigmentation No Not much Yes YesLess hair No Not much Yes YesScaling skin No No Not much Yes
PBS Late DT
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4. Early DT and Full DT groups have high effector Tcell (Teff), Langerin- myeloid numbers and LCactivation on postnatal day 28.
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Teffs (Abs No)
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Tregs (Abs No)
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Langerin- (Abs No)
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LCs (Abs No)
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CD4+ (Abs No)
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ILCs (Abs No)
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MH
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1. Neonatal Tregs are required for pigmentation and maintenance of hair follicles2. Depletion of Tregs causes immediate transcriptomic changes associated with neurobiology.3. Absence of Tregs during P6-P8, but not P10-P12, causes skin defects.4. Elevated Teff and Langerin- myeloid number, as well was activated LCs, may contribute to skin defects.5. We will assess how cytokines, secreted by Teffs, affect neuronal innervation of hair follicles.
DorsalP6 P8 P10 P12 P28
Harvest
LCs
