Blocking immune memory cells can cure vitiligo

20 July 2018

By blocking the survival of ‘memory’ immune cells, researchers have found a cure for vitiligo, an autoimmune condition in which the the immune system attacks the pigment-producing cells of the skin, leaving beihind characteristic pale patches...

Although not dangerous in itself, vitiligo is a disease that can be disfiguring, causing a great deal of distress to people suffering from this condition. Although there are treatments available for vitiligo, including topical creams that suppress the immune attack on skin cells, and phototherapy, which uses UV light, they are time- and effort- consuming: Multiple treatment sessions are required on a regular basis, particularly when large areas of skin are affected. Additionally, these treatments only work to re-pigment the skin temporarily, with the disease invariably recurring in patients after any therapy is stopped. Crucially, when the diseasereturns, this tends to happen in the same patches of skin where it first appeared.

This suggestion that the disease has some sort of ‘memory’ for where it has previously occurred prompted a team of researchers, led by John Harris at the University of Massachusetts Medical School, to look into this property further. It is known from viral infections in the skin that once the infection is cleared, the immune system leaves behind so-called ‘resident memory T cells’, a type of immune cell which can ‘remember’ the offending virus, recognising it and attacking it promptly should it be found in the skin again. "Based on the fact that these cells form to help fight viruses a second time," says Harris, "we thought that they might form in autoimmunity as well in a similar way, and that they could be the source of this return of white spots to the same location."

The team looked at skin samples from patients, but also from a mouse model developed for vitiligo. In both cases, the researchers found what they were looking for: resident memory T cells.

Given these memory T cells are ubiquitously present in the white patches, does this mean they could hold the answer to a cure? "We thought that if we could remove those cells, not only would the skin get better but it might stay better" says Harris. :We were looking for an ‘Achilles' heel’ in these cells, and we found that a protein called IL-15 was needed for their survival in the skin. So we thought that if we cut off that survival signal, the cells would go away - and we found that to be true. When we blocked IL-15 signalling in the mice, the white patches disappeared.”

Interestingly, it appeared that even if the mice were treated for a relatively short period of time - a few weeks - their symptoms continued to improve for months, suggesting that this form of treatment could provide a long-term cure.

But if these resident memory T cells have also have a role in fighting infection, might it not be risky to block their survival? It appears from the study that this may not be a problem. "We were a little surprised to find that the vitiligo-specific resident memory T cells appeared to rely more on IL-15 than the T cells that fight infection the vitiligo-causing T cells disappeared, but the others did not," explains Harris, "so we’re hopeful that not only will this be an effective medical treatment, but that it will also be safe."

Crucially, if blocking resident memory T cells proves effective in treating vitiligo, it may have applications in other autoimmune diseases as well. "Patients with vitiligo and their families are at an increased risk of developing a number of other autoimmune diseases. We think this suggests that they run on the same pathways - that they use the same fuel to operate," says Harris. "So our hope is that by studying vitiligo, not only will we help patients with vitiligo, but we may be able to develop drugs that will work on these other diseases as well."

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