Choreographing Immunity in the Skin Epithelial Barrier.

The skin interfaces with the external environment and is home to a myriad of immune cells that patrol the barrier to ward off harmful agents and aid in tissue repair. The formation of the cutaneous immune arsenal begins before birth and evolves throughout our lifetime, incorporating exogenous cues from microbes and inflammatory encounters, to achieve optimal fitness and function. Here, we discuss the context-specific signals that drive productive immune responses in the skin epithelium, highlighting key modulators of these reactions, including hair follicles, neurons, and commensal microbes. We thus also discuss the causal and mechanistic underpinning of inflammatory skin diseases that have been revealed in recent years. Finally, we discuss the non-canonical functions of cutaneous immune cells including their burgeoning role in epithelial regeneration and repair. The rapidly growing field of cutaneous immunity is revealing immune mechanisms and functions that can be harnessed to boost skin health and treat disease.

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Eavesdropping on the conversation between immune cells and the skin epithelium

The skin epithelium covers our body and serves as a vital interface with the external environment. Here, we review the context-specific interactions between immune cells and the epithelium that underlie barrier fitness and function. We highlight the mechanisms by which these two systems engage each other and how immune–epithelial interactions are tuned by microbial and inflammatory stimuli. Epithelial homeostasis relies on a delicate balance of immune surveillance and tolerance, breakdown of which results in disease. In addition to their canonical immune functions, resident and recruited immune cells also supply the epithelium with instructive signals to promote repair. Decoding the dialogue between immunity and the epithelium therefore has great potential for boosting barrier function or mitigating inflammatory epithelial diseases.

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Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease.

Stem cells regenerate tissues in homeostasis and under stress. By taking cues from their microenvironment or “niche,” they smoothly transition between these states. Immune cells have surfaced as prominent members of stem cell niches across the body. Here, we draw parallels between different stem cell niches to explore the context-specific interactions that stem cells have with tissue-resident and recruited immune cells. We also highlight stem cells’ innate ability to sense and respond to stress and the enduring memory that forms from such encounters. This fascinating crosstalk holds great promise for novel therapies in inflammatory diseases and regenerative medicine.

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Wound, heal thyself

Naik S. Nature Medicine. 24, 1311–1312 (2018)

An in vivo cellular reprogramming strategy to generate epithelial cells from wound mesenchymal cells promotes healing and provides a new avenue for the treatment of nonhealing wounds.

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The healing power of painful memories

Naik, S. The healing power of painful memories. Science 359(6380): 1113 March 2018

Our body’s epithelia are barriers that interface with the terrestrial environment and routinely experience inflammation. Although a vast majority of these inflammatory reactions resolve, they imprint the tissue with a memory. Cells of the immune system are traditionally thought to be the bearers of this memory, allowing them to react faster to subsequent inflammatory pressures (1, 2). Yet, barrier tissues are composites of epithelial, mesenchymal, nervous, vascular, and immunological networks working in unison to sustain optimal function in health and disease. The question of whether tissue-resident cells, distinct from the immune system, are entrained in response to a perturbation remains to be addressed.

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