Investigating the role of lipids in scalp inflammation

The scalp is a complex immunological niche with a densely populated immune system, able to sense and react to danger signals. The epidermis and dermis contain high numbers of tissue-resident T cells including lipid-reactive T cells which play a central role in the pathogenesis of skin diseases including psoriasis and atopic dermatitis. The pathogenic functions of lipid-reactive T cells have been associated with the dysregulation of lipid synthesis and metabolism linked to these diseases, resulting in their activation and subsequent initiation of an inflammatory cascade.

Nonetheless the specific lipids and signals controlling T cell activation in the skin and how those underpin inflammation remain unclear.

It is becoming clear that many skin disorders have underlying microbial contribution. For instance, atopic dermatitis is associated with colonization with S. aureus, while changes in Malassezia and Staphylococcus levels are found in dry skin and dandruff. Interestingly, many of these microorganisms secrete lipases that can contribute to the altered lipid composition associated with these conditions and subsequent T cell activation and inflammatory responses.

Lipidomic and transcriptomic analyses (performed in Unilever) have unveiled changes in lipid composition and metabolism in dandruff vs healthy scalp suggesting a role for lipid-reactive T cells in cosmetic skin disorders. Moreover, recent data from our lab has confirmed that both inflammatory stimuli and commensal species alter the lipidome and metabolic pathways of human Langerhans cells (LC, a skin resident myeloid antigen presenting cell) resulting in activation of lipid-reactive T cells.

In this project we will capitalize on this recent discovery to identify lipid pathways that can be targeted to modulate scalp inflammation.