Newswise — Boston, MA -- Chemical compounds found in skin creams and other personal care products can cause an allergic reaction in the skin, a common condition known as allergic contact dermatitis (ACD). While ACD is on the rise, particularly in industrialized countries, exactly how personal care chemical compounds trigger a reaction remains unknown. Most allergic reactions involving T cells are attributed to proteins or peptide antigens that trigger the immune system. But chemical compounds found in personal care products are different kinds of molecules that were not thought to be able to directly elicit a reaction by T cells. Investigators from Brigham and Women's Hospital, Columbia University and Monash University have uncovered a new molecular mechanism by which common components of consumer products can trigger an immune response, highlighting a specific molecular connection that may explain the mystery behind these cases of ACD. The team's findings are published in Science Immunology.
"What we present here is a molecular missing link," said co-senior author D. Branch Moody, MD, a principal investigator and physician in the Brigham's Division of Rheumatology, Inflammation and Immunity. "We questioned the prevailing paradigm that T cell-mediated allergic reaction is only triggered when T cells respond to proteins or peptide antigens. We find a mechanism through which fragrance can initiate a T cell response through a protein called CD1a."
For many substances, such as those found in soaps, cosmetics, fragrances, jewelry and plants, it is unclear how a reaction by T cells is triggered. Chemical compounds found in these products were thought to be too small and of the wrong chemical structure to be detected directly by T cells, which are the immune cells that set off ACD.
The researchers, including the co-lead author Annemieke de Jong from Columbia University, wondered if there might be another explanation. The team tested whether CD1a, a molecule found in immune cells that form the outer layer of human skin, could bind directly to allergens found in personal care products and present these molecules to the immune system, triggering a reaction. First author, Sarah Nicolai, MD, a research fellow in Medicine at the Brigham, exposed T cells to material from skin patch testing kits used in allergy clinics and found that T cells responded to certain substances, including balsam of Peru, a tree oil widely used in cosmetics and toothpaste. The team further identified substances within balsam of Peru -- benzyl benzoate and benzyl cinnamate -- directly responsible for stimulating the T cell response. Investigators also tested similar substances and found a dozen small molecules, including farnesol, that appeared to elicit a response.
To further understand how these compounds triggered a reaction, investigators at Monash University solved the X-ray crystal structure, revealing that when farnesol forms a complex with CD1a, farnesol kicks out naturally occurring human lipids, making CD1a more visible to T cells and leading to T cell activation.
The authors note that while their work shows that fragrances found in personal care products can directly initiate a T cell response, further investigation is needed to understand if this causes disease and allergic reactions. To better understand this, they will need to see if patients commonly have T cells that recognize molecules like farnesol. The team is also seeking new molecules that could block the response of CD1a and override the activation of T cells. Work is currently underway to identify promising molecules.
The research was funded by grants from the National Institutes of Health (T32 AI007306, K01 AR068475, R01 AR048632), the National Health and Medical Research Council of Australia (NHMRC), and the Australian Research Council (ARC) (CE140100011); an Irving Scholarship from the Irving Institute for Clinical and Translational Research at Columbia University, and a Wellcome Trust Collaborative Award. Research reported in this publication was performed in the CCTI Flow Cytometry Core, supported in part by the Office of the Director, National Institutes of Health, under award S10OD020056.
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