Researchers at Yale School of Medicine have demonstrated that Langerhans cells in the skin, which had been thought to alert the immune system to pathogens, instead dampen the skin's reaction to infection and inflammation.
This has the potential to significantly alter understanding of the mechanisms underlying many skin disorders such as psoriasis, lupus and skin cancer.
Dendritic cells are found throughout the body and are extremely efficient at alerting the immune system to the presence of pathogens and other foreign materials. Langerhans cells are dendritic cells in the skin. Skin is an important barrier to infection and it has been generally assumed that the Langerhans cells only serve to warn the immune system of skin pathogens.
According to the study, featured on the cover of the December 15 issue of Immunity, Langerhans cells are not required and, in fact, inhibit or modulate immune responses in the skin.
Daniel H. Kaplan, M.D., and Mark J. Shlomchik, M.D., used a technology called Bacterial Artificial Chromosome transgenics to develop a mouse model that lacks Langerhans cells in the skin from birth. They stimulated the skin of these mice to create hypersensitivity similar to a poison ivy reaction. They expected that mice without Langerhans cells would have less immune response in the skin.
"Unexpectedly, instead of a decreased immune response to contact hypersensitivity, we found a reproducible and significant increase," said first author Kaplan, assistant professor in the Department of Dermatology at Yale School of Medicine. "Langerhans cells are thus not required to generate immune responses in the skin and more profoundly, they actually regulate immune responses in the skin."
According to senior author Shlomchik, professor of laboratory medicine and immunobiology at Yale, "We now have a new view of these cells, not just as sentinels or stimulators of immune reactions as previously thought, but more as peacekeepers with the environment, which poses a constant challenge to skin. Most such challenges are not dangerous and do not warrant an immune response."
Langerhans cells may function generally to prevent excessive responses in the skin. "Failure of this mechanism could result in chronic inflammatory skin conditions like lupus and psoriasis, said Shlomchik. "This is the new theory we would now like to test."
The findings could also have future implications for skin transplantation, autoimmune diseases and the immune system's ability to prevent skin cancer.
Other authors on the study included Mathew C. Jenison, Sem Saeland and Warren D. Shlomchik.
The study was funded by the National Institutes of Health through the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Dermatology Foundation.
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