Chronic inflammation may turn skin-protecting antibody into a tumour promoter
The Immunoglobulin E (IgE) antibody is commonly found in healthy skin and believed to protect against harmful substances or parasitic infections; however, a mouse-model study published online ahead of print in eLife (Jan. 14, 2020) shows that chronic inflammation caused by repeated exposure to skin-irritating chemicals may turn this helpful defence into a harmful one.
Researchers in the department of immunology and inflammation at Imperial College in London believe a better understanding of this process could help scientists develop ways to prevent or treat skin cancer.
"Chronic inflammation has been linked to many types of cancers, and may cause these by enabling the growth and survival of cells with cancer-causing mutations," said Dr. Mark Hayes, the study's lead author, in a press release. Dr. Hayes was a postdoctoral scientist in the department of immunology and inflammation at Imperial College at the time of the study. "But the exact steps in this process and the role of IgE were not previously clear."
Dr. Hayes and his colleagues studied what happened after inflammation-causing substances were applied to the skin. The researchers saw an increase in the amount of IgE produced and that basophils were attracted to the skin. When the basophils were activated by IgE, they stimulated skin cells to divide and grow.
"IgE fortifies the skin barrier defences by promoting cell growth to thicken the surface of the skin in response to noxious stimuli," Dr. Hayes said. "However, this response should be temporary. If it persists in the long term, it may lead to tumour growth."
Researchers discovered that in mice with cancer-causing mutations, chronic activation of IgE caused by inflammation ruins its protective effects and helps the growth of precancerous skin cells into tumours. On the other hand, mice lacking IgE were protected from developing these tumours in response to inflammation.
A previous study by Dr. Hayes and his colleagues showed that IgE protects mice against cancer-causing substances that damage DNA. This suggests that the mechanism of tumour growth, and the role of IgE in this process, may depend on different kinds of environmental exposure.
"Our previous and current findings reveal a strong link between IgE and cancer," said Dr. Jessica Strid, one of the study's senior authors. Dr. Strid is a reader in cellular immunology in the department of immunology and inflammation at Imperial College. "But the biological consequences of IgE engagement in the skin clearly depends on the nature of the antibodies and the microenvironment in which the tumour grows."