How the Skin Reacts to the Environment

-From 2016, articles commented in the Journal and Focus will be posted here (selection by Prof. JH Saurat M.D.)

How the Skin Reacts to the Environment

Postby CFH » Thu Dec 01, 2016 2:44 am

In Situ Mapping of Innate Lymphoid Cells in Human Skin: Evidence for Remarkable. Differences between Normal and Inflamed Skin. In Situ Mapping of Innate Lymphoid Cells in Human Skin: Evidence for Remarkable Differences between Normal and Inflamed Skin.
Brüggen MC, Bauer WM, Reininger B, Clim E, Captarencu C, Steiner GE, Brunner PM, Meier B, French LE, Stingl G.
J Invest Dermatol. 2016 Dec;136(12):2396-2405. doi: 10.1016/j.jid.2016.07.017.


Innate lymphoid cells (ILCs) are the most recently identified cell types to be added to the complex cellular map of the immune system.

-Their role in the skin is incompletely understood but in the mucous surface of lung and intestines, they regulate barrier function. Because of their location as the first to be put in contact with the exterior environment they likely play a role in mounting the inflammatory response in addition to tissue development, integrity and homeostasis.


In this Swiss and Austrian study, the authors sought to explore the presence of this immune cell in the skin and imply its potential role. They compares the presence of these cell types in inflamed vs normal skin.
-Atopic Dermatitis and Psoriasis are the most commonly encountered inflammatory skin diseases
infiltrate ILC innate lymphoid cells. 13 biopsies were taken in lesional skin in AD and P and matched with healthy controls

RESULTS
The presence of ILC were revealed with immunofluoresence
-normal skin contained scarce numbers of ILC (ILC1 and AhRILC3)
-Atopic skin contained ILC2 and prominent AhR+ILC3 = this could suggest an increased sensitivity to environmental factors (see DH10 December 2016 issue)
-Psoriasis skin contained ILC1s and RORC+ILC3s

ILCs were found to be located high up in the epidermis in close proximity to T lymphocytes

ILCs: "to gauge the environment"
-ILCs contain nuclear receptors including Aryl Hydrocarbon Receptor (AhR). It is therefore possible that ILCs sense environmental agents such as pollutants. (ILC3).
-The diagram below shows the type of pathways ILC3 uses to respond to stimuli including through AhR receptor, it then mounts inflammatory responses through activation of several pathways.

Potential Roles of ILCs:
-ILCs promote protective immunity to pathogens
-ILCs in allergy and autoimmunity
-Organogenesis and maintenance of tissue integrity
-ILCs and cancer
-ILCs and metabolic homeostasis

Why pay attention to ILCs ?
-The identification of various ILC subsets and further insight into their tissue distribution have highlighted important functions for ILCs in triggering immunity, inflammation and tissue repair.
-ILC1s, ILC2s and ILC3s have multiple interactions with the microbiota, nutrients, metabolites, neurons and parenchymal cells.
-The molecular mechanisms underlying these interactions and their consequences for tissue homeostasis remain poorly defined.


Additional Reference Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Klose CS, Artis D.Nat Immunol. 2016 Jun 21;17(7):765-74. doi: 10.1038/ni.3489. Review.

CFH
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Innate Lymphoid Cells 3 (ILC3): receptor and subsequent activated pathways
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CFH
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