| First Author | Moreau JM | Year | 2021 |
| Journal | Sci Immunol | Volume | 6 |
| Issue | 62 | PubMed ID | 34452925 |
| Mgi Jnum | J:349740 | Mgi Id | MGI:7645585 |
| Doi | 10.1126/sciimmunol.abg2329 | Citation | Moreau JM, et al. (2021) Regulatory T cells promote innate inflammation after skin barrier breach via TGF-beta activation. Sci Immunol 6(62) |
| abstractText | Regulatory T cells (T(regs)) use multiple mechanisms to attenuate inflammation and prevent autoimmunity. T(regs) residing in peripheral (i.e., nonlymphoid) tissues have specialized functions; specifically, skin T(regs) promote wound healing, suppress dermal fibrosis, facilitate epidermal regeneration, and augment hair follicle cycling. Here, we demonstrated that skin T(regs) were transcriptionally attuned to interact with their tissue environment through increased expression of integrin and TGF-beta pathway genes that influence epithelial cell biology. We identified a molecular pathway where skin T(regs) license keratinocytes to promote innate inflammation after skin barrier breach. Using a single-cell discovery approach, we identified preferential expression of the integrin alphavbeta8 on skin T(regs) Upon skin injury, T(regs) used this integrin to activate latent TGF-beta, which acted directly on epithelial cells to promote CXCL5 production and neutrophil recruitment. Induction of this circuit delayed epidermal regeneration but provided protection from Staphylococcus aureus infection across a compromised barrier. Thus, alphavbeta8-expressing T(regs) in the skin, somewhat paradoxical to their canonical immunosuppressive functions, facilitated inflammation acutely after loss of barrier integrity to promote host defense against infection. |
