TY - JOUR T1 - Interactions Between Epidermal Keratinocytes, Dendritic Epidermal T-Cells, and Hair Follicle Stem Cells. JF - Methods Mol Biol Y1 - 2019 A1 - Badarinath, Krithika A1 - Dutta, Abhik A1 - Hegde, Akshay A1 - Pincha, Neha A1 - Gund, Rupali A1 - Jamora, Colin AB -

The interplay of immune cells and stem cells in maintaining skin homeostasis and repair is an exciting new frontier in cutaneous biology. With the growing appreciation of the importance of this new crosstalk comes the requirement of methods to interrogate the molecular underpinnings of these leukocyte-stem cell interactions. Here we describe how a combination of FACS, cellular coculture assays, and conditioned media treatments can be utilized to advance our understanding of this emerging area of intercellular communication between immune cells and stem cells.

VL - 1879 ER - TY - JOUR T1 - PAI1 mediates fibroblast-mast cell interactions in skin fibrosis. JF - J Clin Invest Y1 - 2018 A1 - Pincha, Neha A1 - Hajam, Edries Yousaf A1 - Badarinath, Krithika A1 - Batta, Surya Prakash Rao A1 - Masudi, Tafheem A1 - Dey, Rakesh A1 - Andreasen, Peter A1 - Kawakami, Toshiaki A1 - Samuel, Rekha A1 - George, Renu A1 - Danda, Debashish A1 - Jacob, Paul Mazhuvanchary A1 - Jamora, Colin AB -

Fibrosis is a prevalent pathological condition arising from the chronic activation of fibroblasts. This activation results from the extensive intercellular crosstalk mediated by both soluble factors and direct cell-cell connections. Prominent among these are the interactions of fibroblasts with immune cells, in which the fibroblast-mast cell connection, although acknowledged, is relatively unexplored. We have used a Tg mouse model of skin fibrosis, based on expression of the transcription factor Snail in the epidermis, to probe the mechanisms regulating mast cell activity and the contribution of these cells to this pathology. We have discovered that Snail-expressing keratinocytes secrete plasminogen activator inhibitor type 1 (PAI1), which functions as a chemotactic factor to increase mast cell infiltration into the skin. Moreover, we have determined that PAI1 upregulates intercellular adhesion molecule type 1 (ICAM1) expression on dermal fibroblasts, rendering them competent to bind to mast cells. This heterotypic cell-cell adhesion, also observed in the skin fibrotic disorder scleroderma, culminates in the reciprocal activation of both mast cells and fibroblasts, leading to the cascade of events that promote fibrogenesis. Thus, we have identified roles for PAI1 in the multifactorial program of fibrogenesis that expand its functional repertoire beyond its canonical role in plasmin-dependent processes.

VL - 128 IS - 5 ER - TY - JOUR T1 - Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of γδT-cells. JF - Elife Y1 - 2017 A1 - Lee, Pedro A1 - Gund, Rupali A1 - Dutta, Abhik A1 - Pincha, Neha A1 - Rana, Isha A1 - Ghosh, Subhasri A1 - Witherden, Deborah A1 - Kandyba, Eve A1 - MacLeod, Amanda A1 - Kobielak, Krzysztof A1 - Havran, Wendy L A1 - Jamora, Colin AB -

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 , 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.

VL - 6 ER -