Figure 2.

Reparative role of tissue-resident Treg. (A) Treg can promote repair through direct interaction with tissue progenitor cells. Skeletal muscle-resident Treg promotes the conversion of M1 to M2 macrophages, and the timely switch is important in muscle repair, as M1 macrophages are responsible for inducing proliferation of myogenic precursor cells, whereas M2 macrophages promote the differentiation of myogenic precursor cells. Skeletal muscle-resident Treg also releases AREG which stimulates the differentiation of satellite cells. Lung-resident Treg releases AREG and KGF, and AREG is important lung tissue repair post-influenza infection, whereas KGF induces the proliferation of AT2 cells in the alveolar epithelium. Gut-resident Treg releases IL-10 promotes the self-renewal of stem cells in the intestinal epithelium. Skin-resident Treg in hair follicles can induce the proliferation and differentiation of hair follicle stem cells through Jag1/Notch interaction. (B) Treg interact with supportive cells to create an appropriate stem cell niche for tissue repair. Skin-resident Treg inhibit the CXCL5/Th17/neutrophil axis, which includes Th17 releasing IL-17A, IL-17A inducing the release of CXCL5 by keratinocyte, and CXCL5 recruiting neutrophils. The overall effect of the inhibition of the axis is the migration of hair follicle stem cells to the upper epidermis and their differentiation into keratinised epithelial cells for repair of the skin barrier (Adapted with permission from ⁵⁰, copyright 2019 Elsevier Inc.). Nerve-resident Treg releases CCN3, which is thought to promote oligodendrocyte differentiation, and thus the remyelination of neurones in the central nervous system. Bone marrow-resident Treg regulates the release of IL-7 from ICAM1⁺ perivascular stromal cells, which supports the development of lymphoid lineage including the differentiation of B cells from haematopoietic stem cells (Adapted with permission from ⁵², copyright 2017 Nature Research).