Understanding immune responses to lipids in the skin

The skin is a complex immunological niche containing high numbers of tissue-resident T cells that regulate skin homeostasis and protect from external insults. Amongst the families of tissue-resident lymphocytes, CD1-restricted lipid-reactive T cells play a central role in the pathogenesis of skin diseases including psoriasis and atopic dermatitis. The pathogenic functions of CD1-restricted T cells have been associated with the dysregulation of lipid synthesis and metabolism linked to these diseases, resulting in the activation of lipid-reactive T cells that in turn initiate an inflammatory cascade. Lipidomic and transcriptomic analyses (performed in Unilever) have unveiled changes in lipid composition and metabolism in dandruff vs healthy skin suggesting a role for lipid-reactive T cells in cosmetic skin disorders. Nonetheless, the complex interplay between lipid metabolism and the regulation of skin immunity remains poorly understood.
An essential component of human skin is the skin microbiome. In fact, it is becoming clear that many skin disorders have an underlying microbial contribution. For instance, atopic dermatitis is associated with colonization with S. aureous, P. acnes is associated with acne, while changes Malassezia and Staphylococcus are found in dry and dandruff skin. Interestingly, many of these microorganisms secrete lipases that may contribute to the altered lipid composition associated to these conditions. However, how skin microorganisms modulate local immunity in skin homeostasis and disease remains virtually unexplored.