Vitiligo is an autoimmune disease in which the body’s immune system attacks and destroys melanocytes, the cells that produce the skin pigment melanin. The loss of melanocytes causes the skin to turn white, resulting in the characteristic skin patches of this disease.
However, the standard model of vitiligo does not account for some of its unusual features. Some vitiligo lesions repigment, and treatment may restore pigmentation in areas lacking melanocytes, suggesting that melanocytes may not be completely destroyed.
A research team at Osaka Metropolitan University led by Project Professor Ichiro Katayama and Project Associate Professor Yang Ling-Li has found evidence that melanocytes do not completely disappear from skin with vitiligo and enter a “dedifferentiation-like state” in which mature cells revert to a more primitive form and lose many of their specialized functions, such as pigment production.
This study reveals a new mechanism underlying the development of vitiligo and may change the treatment of this disease. ”
Dr. Lingli Yang Specially Appointed Associate Professor, Osaka Metropolitan University
Their study joins a growing body of research showing that cells not only respond to chemical signals, but also to what’s physically attached to them. Melanocytes are located on the basement membrane, a thin layer that separates the epidermis and dermis, providing instructions for melanocytes to maintain functional pigment-producing cells.
However, in patients with vitiligo, the extracellular matrix surrounding melanocytes is remodeled. Melanocytes normally bind laminin-211. However, in patients with vitiligo, the basement membrane becomes enriched with laminin-332. As a preferred binding partner becomes unavailable, melanocytes change their binding methods. They attach via integrin α3β1 instead of using their preferred attachment substance, dystroglycan.
These changes activate pathways that are commonly activated when cells remodel. This process reorganizes the cell’s actin cytoskeleton and changes gene expression, including genes associated with the immature melanocyte state. This finding suggests a self-reinforcing cycle in which basement membrane changes promote melanocyte dedifferentiation, while dedifferentiated melanocytes are no longer able to maintain a healthy basement membrane, further promoting the disease process.
“This was an exciting discovery for us, as most current treatments mainly focus on suppressing autoimmune attacks and reducing inflammation. However, if dormant melanocytes are still present in the lesions, it may change the way we treat the disease,” Professor Katayama said. “New therapeutic avenues may become possible, such as reactivating existing cells or restoring their normal attachment to the basement membrane.”
When researchers used pharmacological inhibitors that targeted the signaling pathways activated by this adhesion switch, they were able to restore expression of mature melanocyte markers, restore expression of pigmentation-related genes, and reverse many features of the dedifferentiation-like phenotype.
“This was an interesting aspect of our study because it suggests that changes in gene expression are not permanent and that this process may be reversible,” Dr. Yang explained. “We found that the drug can restore melanocyte function and pigmentation-related characteristics. The next step is to conduct clinical studies to see if this approach is a viable way to manage the disease.”
sauce:
Osaka Metropolitan University
Reference magazines:
Yang, F. Others. (2026). Aberrant laminin signaling promotes melanocyte dedifferentiation and reveals a tractable therapeutic target in vitiligo. nature communications. DOI: 10.1038/s41467-026-72064-w. https://www.nature.com/articles/s41467-026-72064-w.
