"Impact of the skin microbiome on a novel immune-sebum phenotype"

Jordan Harris, Ruth Choa, Elizabeth Grice and Taku Kambayashi

Sebum provides vital cutaneous functions including moisture retention and defense against pathogens. Despite the well-defined immunologic function of sebum, immune system involvement in sebum regulation is unknown. Sebum hypersecretion predisposes to the common condition acne vulgaris for which current therapeutics can be harmful and ineffective. There is a critical need for research into additional mediators of sebum secretion. We found that the keratinocyte-derived cytokine thymic stromal lymphopoietin (TSLP) promotes sebum secretion through T cell stimulation. TSLP- and T cell-deficient mice display reduced sebum secretion, suggesting an immunologic role in sebum homeostasis. Why does this circuit exist? Analogous intestinal studies show goblet cell mucus secretion acting as an immunologic mediator by regulating growth of gut microbiota. A similar circuit may exist in the skin. I hypothesize that the skin microbiome induces TSLP-mediated, microbial-specific T cell-dependent sebum secretion, acting as a homeostatic defense against cutaneous infection. To investigate if skin microbiome presence is necessary for sebum secretion, I used germ-free (GF) models to deplete the skin microbiome. I found that GF mice secrete less sebum at baseline. Sebum secretion was not rescued with microbiota conventionalization in adult mice. I attempted to conventionalize neonatal GF mice, as early-life immune-microbe interactions have been shown to initiate multiple immune functions. Similarly, sebum secretion was not rescued. Overexpressing TSLP in GF mice and transferring control T cells to GF RAG KO mice did not increase sebum secretion, suggesting the sebaceous gland (SG) response may be dysfunctional. TSLP overexpression leads to SG size reduction in control, but not GF mice. I plan to stain GF SGs for functional markers and perform RNA sequencing to identify how GF SGs are dysfunctional. By studying this homeostatic immune-sebum circuit, novel therapeutic targets for sebum-dysregulation diseases may be identified and utilized to improve patient health and quality of life.