Tag: vitiligo

Microbial Therapy Offers New Hope for Vitiligo Patients

Photo by Hanen BOUBAHRI on Unsplash

A natural compound derived from gut-friendly bacteria significantly slows the progression of vitiligo and may restore pigmentation, reports a new Northwestern University pre-clinical study in mice. 

The findings, published in the Journal of Investigative Dermatology, could offer hope to millions affected by the autoimmune disease, which causes visible patches of skin discoloration and carries profound emotional and physical consequences.

“The results in our model were astonishing,” said senior study author I. Caroline Le Poole, a professor of dermatology and microbiology-immunology at Northwestern University Feinberg School of Medicine. 

“We found that administering a microbial compound weekly to vitiligo-prone mice significantly suppressed disease progression. It made a spectacular difference in an aggressive model of the disease.”

What is vitiligo?

Vitiligo affects 0.5% to 2% of the global population and is linked to other health challenges, including higher risks of cardiovascular disease, psychological distress and endocrine disorders.

Discoloration often appears on the face, scalp, hands and arms, as well as around body openings like the mouth and genitals. Many individuals with vitiligo also have at least one other autoimmune condition.

How the study was conducted

Le Poole and her colleagues administered a microbial product weekly to vitiligo-prone mice over an 18-week period. By the end, pigment loss on the mice’s backs was reduced by 74%.

The product reduced killer T cells that attack the skin’s pigment and increased protective regulatory T cells, which are typically scarce in vitiligo patients.

“This simple microbial compound could work as a standalone therapy, or in synergy with existing treatments,” Le Poole said.

Existing therapy has limitations

In 2022, the FDA approved the first re-pigmentation therapy for vitiligo: Opzelura (ruxolitinib) cream. Clinical trials found that only 30% of patients using the cream regained 75% or more skin re-pigmentation on the face.

“Our findings about the effectiveness of microbial therapy could give hope to patients who are not well-served by existing treatments,” Le Poole said.

Vitiligo is more severe in patients with darker skin

Le Poole, who has spent more than 30 years studying vitiligo, said the disease has been found to be more severe in people with darker skin tones. The visibility of the discolouration in people with darker skin can also amplify stigma and emotional distress. 

“Patients often feel powerless as they watch their disease progress, unsure how they will look next month,” Le Poole said. “For many, stabilising the disease would be life changing.” 

While the disease can affect self-esteem – particularly for adolescents navigating social pressures – some people embrace it.

“We’ve seen beautiful models with vitiligo challenging societal norms, and that’s wonderful,” Le Poole added. “But for those who want treatment, it’s important to provide real options that can halt disease progression.”

Next steps

The next challenge is adapting the microbial product for human use. “Weekly injections could work, but we need to explore simpler options, like a food additive or ointment,” said Le Poole. “We also need to understand how long the effects last and the best timing for treatment.”

Le Poole added that the same microbial compound she and her colleagues injected in mice could potentially treat other autoimmune conditions, particularly those involving killer T cells in the skin.  

“Our next step is collaborating with scientists from several institutions to refine the compound, understand its mechanisms and determine whether it works alongside existing treatments for auto-immune disease.”

Source: Northwestern University

New Therapy Eliminates ‘Problematic’ T Cells in Skin Autoimmune Diseases

Photo: CC0

In a groundbreaking study published in Science, researchers discovered distinct mechanisms controlling different types of immune cells, and found that, by precisely targeting these mechanisms, they could selectively eliminate ‘problematic cells’ and reshape the skin’s immune landscape.

The skin is packed with specialised immune cells that protect against infections and cancer and promote healing. These cells, called tissue-resident T cells or TRM cells, stay in place to fight infections and cancerous cells in the skin.

However, when not controlled properly, some of these skin TRM cells can contribute to autoimmune diseases, such as psoriasis and vitiligo.

Researchers, led by University of Melbourne’s Professor Laura Mackay, a Laboratory Head and Immunology Theme Leader at the Peter Doherty Institute of Infection and Immunity (Doherty Institute), found a way to redress this imbalance.

University of Melbourne’s Dr Simone Park, an Honorary Research Fellow and former Postdoctoral Fellow in the Mackay Lab at the Doherty Institute, and lead first author of the study, said that this research is the first to describe the unique elements that control various types of skin TRM cells in animal models, offering precise targets for potential treatment strategies.

“Specialised immune cells in our skin are diverse: many are critical to prevent infection and cancer, but others play a big role in mediating autoimmunity,” said Dr Park.

“We discovered key differences in how distinct types of skin T cells are regulated, allowing us to precisely edit the skin’s immune landscape in a targeted way.”

University of Melbourne’s Dr Susan Christo, Senior Research Officer in the Mackay Lab at the Doherty Institute and co-first author of the study, explained how these discoveries could advance efforts to treat skin disease.

“Most autoimmune therapies treat the symptoms of the disease rather than addressing the cause. Conventional treatments for skin disorders often impact all immune cells indiscriminately, meaning that we could also be wiping out our protective T cells,” said Dr Christo.

“Until now, we didn’t know how to pick apart ‘bad’ T cells in the skin from the ‘good’ protective ones. Through this research, we discovered new molecules that allow us to selectively remove disease-causing T cells in the skin.”

The research team harnessed this new knowledge to eliminate ‘problematic’ cells that can drive autoimmune disorders, while preserving the ‘good’ ones that are essential to maintain protective immunity.

University of Melbourne’s Professor Laura Mackay, senior author of the study, explained that these findings could pave the way for more precise and long-lasting therapies for skin disease.

“Skin conditions like psoriasis and vitiligo are difficult to treat long-term. The T cells driving disease are hard to remove, so patients often need life-long treatment. Our approach has the potential to revolutionise the way we treat these skin disorders, significantly improving outcomes for people dealing with challenging skin conditions,” said Professor Mackay.

With the study demonstrating successful removal of specific skin T cells in animal models, further research is necessary to validate the efficacy of these strategies in human subjects.

Dr Park hopes the study will inspire the development of new treatments for skin disease.

“These discoveries bring us one step closer to developing new drugs that durably prevent autoimmune skin disorders without compromising immune protection,” said Dr Park.

Source: The Peter Doherty Institute for Infection and Immunity

Keratinocytes Play a Role in Stable Vitiligo Disease

Targeting keratinocyte metabolism could be a new method of vitiligo treatment. Photo by Hanen BOUBAHRI on Unsplash

A new study published today in JCI Insight reveals the unique cell-to-cell communication networks that can perpetuate inflammation and prevent repigmentation in patients with stable vitiligo disease, and the particular role that keratinocytes play.

“In this study, we couple advanced imaging with transcriptomics and bioinformatics to discover the cell-to-cell communication networks between keratinocytes, immune cells and melanocytes that drive inflammation and prevent repigmentation caused by vitiligo,” said Anand K. Ganesan, MD, PhD, professor at University of California, Irvine. “This discovery will enable us to determine why white patches continue to persist in stable vitiligo disease, which could lead to new therapeutics to treat this disease.”

Vitiligo is an autoimmune skin disease characterised by the progressive destruction of melanocytes by immune cells called autoreactive CD8+ T cells, resulting in disfiguring patches of white depigmented skin. This disease has shown to cause significant psychological distress among patients. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but until now, why the white patches in stable disease persist was poorly understood.

“Until now, the interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools,” said Jessica Shiu, MD, PhD, assistant professor of dermatology and one of the first authors of the study. “By combining non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq), we identified distinct subpopulations of keratinocytes in lesional skin of stable vitiligo patients along with the changes in cellular compositions in stable vitiligo skin that drive disease persistence. In patients that responded to punch grafting treatment, these changes were reversed, highlighting their role in disease persistence.”

MPM is a unique tool that has broad applications in human skin. MPM is a noninvasive imaging technique capable of providing images with sub-micron resolution and label-free molecular contrast which can be used to characterise keratinocyte metabolism in human skin.

Most studies on vitiligo have focused on active disease, while stable vitiligo remains somewhat of a mystery. Studies are currently investigating when metabolically altered keratinocytes first appear and how they may affect the repigmentation process in patients undergoing treatment.

The study findings suggest the possibility of targeting keratinocyte metabolism in vitiligo treatment. Further studies are needed to improve the understanding of how keratinocyte states affect the tissue microenvironment and contribute to disease pathogenesis.

Source: University of California – Irvine