The study, supported by the Milstein Medical Research Program at The Rockefeller University, shows that two immune system molecules play a role in these pigmentation changes.
The researchers were initially looking for further understanding of psoriasis, which is a skin condition that causes red, flaky, crusty patches of skin covered with silvery scales; and the study now has other skin care relevance.
Melanocytes, which give skin its colour, are present in healthy skin but increase during a psoriasis flare-up. When the flare-up subsides, the cells are pushed toward the surface, causing dark marks to appear.
The two immune system molecules, or cytokines, identified as playing a crucial role in skin discolouration are interleukin-17 (IL-17) and tumor necrosis factor (TNF).
It is well-known that these two molecules play an important role in causing the painful rashes that are characteristic of psoriasis, but Claire Q. Wang, a research associate in James Krueger's Laboratory of Investigative Dermatology, wanted to see if the cytokines might also have something to do with the dark spots that psoriasis leaves behind.
Shining new light
"One of the treatments for psoriasis is light therapy," says Wang. "Patients will receive artificial UVA and UVB light as a way to reduce inflammation, and although the light doesn't cause sunburn, it was still commonly assumed that this was causing the pigmentation changes. Our research showed that this was not the case."
The scientists found that the IL-17 and TNF cytokines were disrupting the pigment production of patients' melanocytes – the cells responsible for providing skin with colour.
The researchers also looked at the gene expression of skin cells from people with psoriasis and found decreased expression of the genes involved in pigmentation signaling, correlated with increased amounts of IL-17 and TNF.
The two cytokines were also found to promote the formation of melanocyte clusters and stimulate the production of growth-promoting cytokines.
"Knowing that immune cytokines can change pigment production in melanocytes, while also knowing that chronic inflammation has the potential to increase the number of melanocytes, has clear implications for the design of future therapies to address a set of common skin disorders," says Dr Krueger, director of Milstein Research Program and Dr Martin Carter Professor in Clinical Investigation.
“In addition, the results of this study provide new mechanisms for how abnormal pigmentation associated with some melanocytic nevi and melanomas might arise as a result of immune responses to the growths.”
More work is to be done examining these cytokines’ effect on melanocytes and how this causes skin inflammation.
Claire Q F Wang, Yemsratch T Akalu, Mayte Suarez-Farinas, Juana Gonzalez, Hiroshi Mitsui, Michelle A Lowes, Seth J Orlow, Prashiela Manga, James G Krueger. IL-17 and TNF Synergistically Modulate Cytokine Expression while Suppressing Melanogenesis: Potential Relevance to Psoriasis. Journal of Investigative Dermatology, 2013; 133 (12)