The skin and our immune system

Monday 13 October 2008 8:52AM (view full episode)

Dr Jan Dutz from the Department of Dermatology and Skin Science at the University of British Columbia in Vancouver, Canada, talks about his research into the way the body's immune system works within the skin.


Norman Swan: One of the ways of replacing needles is to use the skin and work in Canada is finding that it may be possible to manipulate the immune system via the skin say for vaccines or anti cancer effects.

Jan Dutz is Associate Professor in Dermatology and Skin Science at the University of British Columbia in Vancouver.

Jan Dutz: Some of the cells that are the orchestrators of immune responses are cells called dendritic cells.

Norman Swan: They are like cells with long sticky tentacles which kind of attract foreign substances and then allow the immune system to be alerted to those substances.

Jan Dutz: Exactly. These cells are the most effective cells in the body at firing up what we call the adaptive immune system. So these are the cells that turn on the immune cells that will kill viruses, that will kill tumours and that will promote the formation of antibodies.

Norman Swan: And it makes a lot of sense that they are in your skin because that's the first stop for many foreign invaders.

Jan Dutz: Exactly, these cells essentially carpet the skin and if we could learn how to manipulate them we would have a handy way of potentially altering immune responses.

Norman Swan: And you've also looked at whether or not the skin is actually a source of auto-immune disease, in other words that's the trigger for the body to attack other parts of itself.

Jan Dutz: OK, systemic lupus erythematosus is a disease where the immune system is overactive and can damage itself.

Norman Swan: Particularly the kidneys, the joints and so on.

Jan Dutz: Yes, but it turns out that a very significant fraction of patients also have skin disease.

Norman Swan: There's a butterfly you can get on your face.

Jan Dutz: Right, in acute lupus one can get a butterfly rash in the face, one can also get scarring hair loss and scarring plaques on the body. Patients with skin lupus can have a predisposition to having overactive immune responses in the skin, even long before they develop the full lupus phenotype.

Norman Swan: And what have you done with that?

Jan Dutz: Well we've known for a number of years that patients with lupus may have a problem in so-called garbage disposal. One of the areas of the body where there's a lot of cell turnover and there are a lot of dead and dying cells is the skin. Patients with lupus may have a problem getting rid of the dead and dying cells in the skin and these cells then become focused for a reaction of the immune system.

Norman Swan: With some autoimmune diseases it's an infection that then triggers an abnormal response. This is more that it's actually a failure of the cells in the body itself.

Jan Dutz: Right but this may happen with the addition of other inflammatory signals which could be provided by infections. So it's probably a one/two hit. There are certain stimuli in the skin such as a sunburn, which may provide both of these factors so a sun burn for example will increase the number of dead cells in the skin, and if you have a tendency to lupus you may not be able to clear those as well. In addition the sunburn causes inflammation which may be similar to an infection or a virus. I mean people with bad sunburn skin can get fevers and can feel horribly ill and in fact we have a mouse model where we take mice that are normally prone to other forms of autoimmunity such as Type 1 diabetes and if we give them repeated sunburns we can switch them over to develop a lupus-like disease. And so that's very useful for studying the early points of when disease may be initiated by the environment.

Norman Swan: And isn't there some evidence that if you already have a skin disease say like eczema you are more vulnerable immunologically?

Jan Dutz: Oh yeah, we now think that systemic allergic reactions -

Norman Swan: When you say systemic you mean in the body itself rather than on the surface?

Jan Dutz: Correct, such as asthma, such as swelling of the throat and such. These severe allergic reactions may have their genesis in the skin. A study in Britain a number of years ago looked at a birth cohort and their hypothesis was that severe peanut allergy was related to something the mums were ingesting when they were pregnant. What they actually found to their surprise was that the highest predictor of getting severe peanut allergy in the children was having atopic dermatitis or eczema when they were very young and having compounds put on their skin that had peanut proteins and allergens. So it seemed that maybe they were getting sensitised to the peanut through the skin and so now there's a movement afoot to try to treat infants with eczema aggressively to maybe prevent what has been called the atopic march, or the progression from inflammation in the skin initially to asthma and more severe systemic sequelae.

Norman Swan: Another way of talking about all that of course is immunisation, in other words you could say that you're immunised to the peanut, you're immunised to the foreign substances that cause psoriasis or indeed systemic lupus but you've been taking that one step further to immunisation itself.

Jan Dutz: Right, with the realisation that these dendritic cells are in the skin we thought it would be very interesting to try and manipulate these dendritic cells to improve vaccine responses. And we've gone about this two different ways - one is to put vaccines directly on the skin and figure out ways of getting those vaccines into the body through the skin in a non-invasive way.

Norman Swan: So what have you done?

Jan Dutz: We've looked at ways of bypassing the barrier of the skin by simple methods such as removing the surface with tape stripping, so just taking off the surface, a painless method which allows us then to vaccinate through the skin. We are looking at developing velcro-like devices with micro needles that can deliver vaccines painlessly through the skin and both of those technologies have preliminary promise. We've shown that we can induce protective immune responses in mice doing this.

Norman Swan: And you've also found that you can add substances to the skin themselves which sensitise and almost alert the system?

Jan Dutz: Yes, we have now figured out that there are chemicals that look like infections and these are called toll-like receptor agonists. The skin has receptors called toll-like receptors which are there to sense danger or potential infection and we can use chemical agents that mimic these infectious agents that are not dangerous but that look like viruses, or look like bacteria and when we put those agents on the skin we can actually improve manyfold the responses to standard vaccines given under the skin or into the muscle even. And we are now pursuing this concept in preliminary human trials.

Norman Swan: Jan Dutz from the University of British Columbia in Vancouver.


Lin JH et al. Pathophysiology of cutaneous lupus erythematosus. Clin Rev Allergy Immunol 2007 oct;33(1-2):85-106

Dutz JP The skin as a site of initiation of systemic autoimmune disease: new opportunities for treatment. J Invest Dermatol 2006 Jun;126(6):1209-12


Associate Professor Jan Dutz
Dermatology and Skin Science
University of British Columbia


Dr Norman Swan
Brigitte Seega