Jagged-1+ skin Tregs modulate cutaneous wound healing.

Skin-resident regulatory T cells (Tregs) play an irreplaceable role in orchestrating cutaneous immune homeostasis and repair, including the promotion of hair regeneration via the Notch signaling ligand Jagged-1 (Jag1). While skin Tregs are indispensable for facilitating tissue repair post-wounding, it remains unknown if Jag1-expressing skin Tregs impact wound healing. Using a tamoxifen inducible Foxp3Jag1 model, we show that loss of functional Jag1 in Tregs significantly delays the rate of full-thickness wound closure.

Human skin CD141 dendritic cells regulate cutaneous immunity via the neuropeptide urocortin 2.

Skin immune homeostasis is a multi-faceted process where dermal dendritic cells (DDCs) are key in orchestrating responses to environmental stressors. We have previously identified CD141CD14 DDCs as a skin-resident immunoregulatory population that is vitamin-D (VitD3) inducible from monocyte-derived DCs (moDCs), termed CD141 VitD3 moDCs. We demonstrate that CD141 DDCs and CD141 VitD3 moDCs share key immunological features including cell surface markers, reduced T cell stimulation, IL-10 production, and a common transcriptomic signature.

Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation-induced tissue damage.

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin.

Treg regulation of the epithelial stem cell lineage.

Tissue repair and maintenance in adult organisms is dependent on the interactions between stem cells (SCs) and constituent cells of their microenvironment, or niche. Accumulating evidence suggests that immune cells, specifically Foxp3 CD4 Regulatory T cells (Tregs), play an important role as a regulator of the SC niche. Undisputedly, Tregs are the major immunosuppressive lineage of the CD4 T cell compartment, and reside within numerous secondary lymphoid organs, where they exert their functions.

Tissue regulatory T cells.

Foxp3  CD4 regulatory T cells (Tregs) are an immune cell lineage endowed with immunosuppressive functionality in a wide array of contexts, including both anti-pathogenic and anti-self responses. In the past decades, our understanding of the functional diversity of circulating or lymphoid Tregs has grown exponentially. Only recently, the importance of Tregs residing within non-lymphoid tissues, such as visceral adipose tissue, muscle, skin and intestine, has been recognized.

Mechanisms, Hallmarks, and Implications of Stem Cell Quiescence.

Cellular quiescence is a dormant but reversible cellular state in which cell-cycle entry and proliferation are prevented. Recent studies both in vivo and in vitro demonstrate that quiescence is actively maintained through synergistic interactions between intrinsic and extrinsic signals. Subtypes of adult mammalian stem cells can be maintained in this poised, quiescent state, and subsequently reactivated upon tissue injury to restore homeostasis.