ScienceDaily (Aug. 25, 2008) — Psoriasis, one of humanity’s oldest known diseases, has also been one of its most misunderstood. But in a new study that could change researchers’ perspective of the skin disorder and potentially lead to powerful new drug targets, Rockefeller University scientists have found that the source of psoriasis may be a single population of inflammatory cells that act as instigators by priming the body’s immune system for self-attack.

Immunity-directing dendritic cells were discovered at Rockefeller in 1973 and, in the years since, researchers have discovered that the cells exist in multiple forms, with different populations residing throughout the body. Discerning the intricacies of each has proven a tricky business.

But when it comes to dendritic cell populations in the skin, Michelle Lowes — assistant professor of clinical investigation in James Krueger’s Laboratory for Investigative Dermatology — and her colleagues have been chipping away at and describing them one by one. Prior work by the researchers had characterized the populations of cells in healthy skin. By comparing those results with skin from psoriasis patients, Lowes, Krueger and their collaborators have found that psoriasis lesions are characterized by a distinctly different composition of dendritic-cell populations: Not only do they have the dendritic cells found in normal skin, but they also have an overabundance of a new variety of “inflammatory dendritic cells” that produce immune-stimulating proteins called cytokines.

In order to see how this new population of cells interact with other immune cells, the researchers first isolated them and then threw them together with T cells. Typically, dendritic cells direct the response of T cells, presenting them with foreign molecules that teach them what to seek and attack. The inflammatory dendritic cells were no different — they triggered activation of the T cells, which promptly began producing more cytokines and other inflammatory proteins. “These cytokines may be important for inducing the psoriasis lesions to develop, or amplifying them,” Lowes says.

The cytokines, and the inflammatory dendritic cells that produce them, all represent possible avenues of exploration for drug designers. Lowes believes that the inflammatory dendritic cells are being called into the skin and may be an ideal target, as they’re a discrete population that doesn’t appear to be required for normal immune activity. “If you could knock them out specifically, you might be able to just treat psoriasis without the unwanted side effects of more general immune suppression,” she says. “And I think that if we could stop the cells from getting into the skin, you may even be able to prevent psoriasis.”

The work could also extend to other autoimmune diseases. “The idea of resident versus inflammatory dendritic cell populations provides a useful model,” she says. “I’m hoping that other investigators will find this model helpful as they look at dendritic cells in different diseases and different organs.” If the cells can be recreated in the lab, they could potentially be used in therapies to boost immunity and increase inflammatory responses against diseases such as cancer.

Journal reference:

1. Zaba et al. Psoriasis Is Characterized by Accumulation of Immunostimulatory and Th1/Th17 Cell-Polarizing Myeloid Dendritic Cells. Journal of Investigative Dermatology, 2008; DOI: 10.1038/jid.2008.194

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Getting under the skin: In the skin of psoriasis patients, most of the dendritic cells are inflammatory (red), as opposed to resident dendritic cells (yellow) that are also found in healthy skin. (Credit: Image courtesy of Rockefeller University)

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