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Discovery Points To The Skin As ‘ground Zero’ For Allergic Disease | Scoop News – Scoop.co.nz

Nov 19th, 2021

Friday, 19 November 2021, 9:07 amPress Release: Malaghan Institute

A ground-breaking discovery from the Malaghan Institutehas shone a light on immune cells in the skin, suggestingthey play a much larger role in the onset of allergies thanfirst thought.

The Immune Cell Biology team

Thediscovery throws into question the long-held belief thatimmune cells behave in the same way, regardless of wherethey are in the body, which has far-reaching implicationsfor allergic and inflammatory conditions.

The paperHomeostatic IL-13 in healthy skin directs dendritic celldifferentiation to promote Th2 and inhibit Th17 cellpolarization, published in Nature Immunology hasfound that dendritic cells in the skin behave differentlythan their counterparts elsewhere in the body. This finding,the cumulation of several years of research supported by theHealth Research Council of New Zealand, thoroughlychallenges the established perception of how these keyimmune cells behave.

Historically, weve assumedthat a dendritic cell in the skin is virtually identical inform and function as a dendritic cell in the lung, saysProfessor Franca Ronchese, whose team led this research.Were only just realising thats not the case, so inmany ways were playing catch up in terms of ourunderstanding and implications indisease.

Dendritic cells act as lookouts andplay an important role in initiating and coordinating immuneresponses. Dendritic cells that live in the skin behavedifferently to dendritic cells anywhere else in the body,and what sets them apart might just be whats driving theformation of allergies with the skin effectivelyground zero for the development of allergicconditions.

This is the most importantimmunological discovery to come out of New Zealand in thepast twenty years, says Malaghan Institute DirectorProfessor Graham Le Gros. It marks a milestone infundamental immunology which will have far-reaching impactsin the design and development of immunotherapies that targetallergic and inflammatory conditions.

Advancementsin technology have played a key role in this shift, withrecent improvements in analytical techniques enablingscientists to determine the subtle but significantdifferences that exist between cells of the sametype.

For most people, these slight differences mightnot be significant, but for the development of allergies,they might make all the difference.

Immune cells rely on uniquechemical signals to inform them about whether and how toreact to potential threats in the body. One of these signalsis called IL-13, a molecule that is made when immune cellsdetect cellular damage caused by allergens or parasiteinfections.

The release of IL-13 acts as a switch,alerting the immune system to the existence of a threat,which results in a cascade of responses that recruit immunecells to the site of infection so the invading organisms canbe destroyed before they cause further damage. This is knownas the inflammatory response.

Until now, immunologistshave assumed that IL-13 was only expressed when absolutelynecessary. After all, too much inflammation can be just asharmful as too little. However, a few years ago ProfRonchese and her team observed something strange; thereseemed to be a constant presence of IL-13 in the skin butnot anywhere else in the body. It took several years ofresearch to determine that this wasnt some randomobservation, but a feature unique to immune cells in theskin.

However, the discovery isnt just an academicnovelty it has real and pressing implications inunderstanding why the skin is often implicated in thedevelopment of allergic conditions.

The skin is unlike any otherorgan in your body. It has to contend with the never-endingassault of undesirable and sometimes dangerous organismsyour body routinely comes into contact with every minute ofevery day. Even sitting in your living room, your skin has afull-time job preventing viruses, bacteria, fungal spores,dust mites and more from taking hold and wreakinghavoc.

When it comes to keeping you safe, the skindoesnt always have the luxury of time to leisurely decidewhich incoming particles are safe, and which ones might makeyou sick. If in doubt, the shoot now, ask questionslater, might be the best approach in terms of keepingyour body safe. After all, its better to trigger theimmune response to something harmless than be caught outletting a deadly virus in through the doors,right?

This priming of the immune response maybe why IL-13 is needed at low but persistent level in theskin, suggests Prof Ronchese. Additionally, these findingssuggest that the immune cells in the skin, particularlydendritic cells, have uniquely adapted to the presence ofIL-13 compared to elsewhere in the body.

However, thedownside to this interplay may mean that the skin is in aconstant tug of war between setting off immune responsesversus not. For most people, this balance is maintainedwithout difficulty. For others, it may be what tips themtowards allergic disease. This is what Prof Ronchese wantsto get to the bottom of.

Its clear that there issomething going on in the immune cells in the skin that isunlike anywhere else in the body. While we have a lot ofwork to do to pinpoint exactly what is happening, we knowthat immune cells in the skin are much more likely toinitiate allergic responses, and we believe that IL-13 is animportant factor in this.

What triggers an allergy can bewide ranging pollen, peanuts, dust, shellfish, petdander. The list goes on. When this triggering becomeschronic, you get allergic disease. Prof Ronchese and Dr MaiaBrewerton, a clinical immunology consultant and collaboratorfor the Malaghan Institutes allergic disease programme,believe the skin is the common factor linking all theseallergies.

As many people living with allergicconditions will attest, most dont suffer from an allergyto just one thing. Rather, allergies tend to accumulate andchange over a lifetime.

Dr MaiaBrewerton

While eczema might not seem as dangerousas a life-threatening peanut allergy, sensitisation in theskin is often the tip of the iceberg the opening of theflood gates for the development of other serious allergicconditions later in life such as food allergy orasthma.

This trend is known as the allergicmarch, and for most people, this march starts in the skinat an early age. Theres not a lot yet known about why theallergic march exists in the first place, or what can bedone to stop it. Generally, scientists agree that theearlier you can prevent the allergies from appearing, theless of a negative effect it will have long term.

Boththe allergic march, and the discovery of IL-13 in the skin,indicate just how important the skin is in determiningwhether or not a person will go on to develop a lifelongbattle with allergic conditions, something Dr Brewerton isintimately familiar with.

Our immune systemisnt born inherently knowing what is and isnt good foryou. Some things your body learns while in the womb andwhile breastfeeding. The rest, your immune system has tolearn on its own one encounter at a time. Just like inreal life, first impressions matter, and how you encountersomething for the first time might make all the differencewhen it comes to developing or preventingallergies.

Take the food we eat, for example. Yourgut, and the immune cells in the gut, have evolved to dealwith all sorts of foods coming and going. It knows whatfood looks like, so knows its not a threat. Butwhat if instead of encountering a food through the gut, theskin is what makes first contact? The immune cells that livethere might not get it right.

What we put on ourskin is crucial, says Dr Brewerton. There isincreasing evidence that early life exposure of food throughthe skin may cause food allergy in susceptible individualsand delaying the introduction of high risk foods like eggand peanut butter in the infant diet increases the chance ofdeveloping a food allergy She has seen first-hand justhow devastating allergies can be for children and theirfamilies, and how difficult it can be dealing with severeallergies on a daily basis.

All too often, allergistssee patients with severe allergies to food found in thingslike skin creams and soaps.

When it comes toallergy, prevention is better than cure says DrBrewerton. I think its really important we considerwhat were putting on our skin, particularly when werevery young or our skin barrier is damaged.

With theNature Immunology paper showing how immune cells inthe skin are dancing on a hair-trigger, Prof Ronchese and DrBrewerton both recommend that parents make sure theirchildren arent unnecessarily excluding important itemsfrom their environment or their diet, and think twice aboutthe products they put on their childs skin.

Yourbody cant learn what is good for it if its neverencountered it, and perhaps we need to consider the mannerin which we introduce these materials to the body, saysProf Ronchese.

Or, as Dr Brewerton puts it, food isfor your mouth, not yourskin.

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Discovery Points To The Skin As 'ground Zero' For Allergic Disease | Scoop News - Scoop.co.nz

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