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Research Report: Loyola University Medical Center
We are trying to understand how stressful conditions can lead to a loss of skin pigmentation. In collaboration with Dr. Boissy’s lab in Cincinnati, we have focused primarily on a chemical known to cause vitiligo in individuals who are sensitive to this compound. This bleaching phenol called 4-tertiary butyl phenol (4-TBP) was already known to suppress pigment formation. At higher concentrations, it can kill pigment cells as well. We found that when pigment cells are exposed to 4-TBP, they defend themselves by making what we call ‘stress proteins’. These stress proteins, besides protecting the cells livelihood, can also tell the body that there is ‘something wrong’. When cells release stress proteins (for example when the cell dies), the stress proteins can activate an immune response. We have shown that a key player in every immune response, the dendritic cell, is activated by stress proteins and gains the ability to kill pigment cells that are under stress. This process by itself can contribute to loss of pigment from the skin. Dendritic cells are also the ‘messenger cells’ of the immune response and can recruit other cells of the immune system to the site. We know for example that T cells can be found in the skin close to remaining pigment cells, but this happens only when the skin is loosing pigment. We are trying to define how these T cells specifically recognize pigment cells, leaving all surrounding cell types alone. We are also interested in defining how important the stress proteins are in perpetuating this process and whether there are ways to intervene so that the immune response to pigment cells can be halted and the loss of skin pigment will stop. For our ongoing studies, it is very important that you are and have been willing to donate your time, your blood and skin tissue. I would like to take the opportunity to invite anyone to tell me their story and/or to offer their participation in our research. I will send you a short questionnaire to fill out and if you live in the Chicago area, we would be very happy to receive your tissue donation. Please contact me at ilepool@lumc.edu for further information. In the meantime, thank you for your continued support of our research. In my lab, we are currently investigating the factors that help precipitate vitiligo. Even if you have the genetic upmake that makes it more likely for you to develop vitiligo, and even if your immune system is ready to target your own pigment cells, it is not clear why you start depigmenting when it happens. For years, you will have an even skin tone until something triggers the vitiligo. Some form of stress, be it directly to the skin or an emotional struggle that indirectly affects skin health, upsets the skin melanocytes and changes their appearance to other cells. In particular, cells of the immune sytem can sense this change and respond by building an immune response that targets the pigment cells of the skin. We have shown that once pigment cells have been exposed to agents that can bleach the skin, they will upregulate the expression of ‘stress proteins’. Part of these proteins wind up in the environment and can activate dendritic cells, the ‘frontier soldiers’ of the immune system. These dendritic cells then enter the skin where they can kill some pigment cells to digest their contents and bring these back to lymphoid organs to launch a major attack on pigment cells. We are deciphering the individual steps involved in this process to come up with steps where we could possibly intervene. For example, it may be possible to capture some of the stress protein before it does damage. The next step we are investigating is how lymphocytes, recruited to the skin by dendritic cells, can specifically recognize the pigment cells in the skin, thereby leaving other cell types unharmed. Besides getting to know the pigment cell, this also involves means of investigating what T cells entering vitiligo skin are recognizing. There are fancy new methods available to investigate this. On the upside of having T cells that efficiently recognize pigment cells is, that normal pigment cells and cells that go astray in malignant melanoma share many properties. That means it is likely, that lymphocytes from vitiligo patients may be very good at recognizing aggressive melanoma tumor cells and if we know more about how they do that, we may be able to exploit these properties and use them to treat patients with this very deadly form of skin cancer For all of these studies, it is very important that you have been willing to send me your stories on vitiligo. And that so any of you have been offering your help by donating skin tissue and blood for us to investigate. If you live in, or sometimes travel to the Chicagoland area and you may be willing to donate tissue, I would love to hear from you. Also, I hope you are willing to fill out the Loyola questionnaire and send it to me as an email attachment, regardless of where you live. My email address is ilepool@lumc.edu . Thank you very much for your continued support of our research! Dr. I. Caroline Le Poole |
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