Dandruff Is a Low‐Grade Inflammatory Condition Featuring Hyperproliferative Keratinocytes, Interleukin‐17‐Producing T Cells, and N‐Acyl Ethanolamines

BACKGROUND: Dandruff features epidermal scaling but lacks overt signs of inflammation, such as erythema. Characterisation of its inflammatory profile may improve understanding of the underlying inflammatory mechanisms and therefore indicate alternative approaches for treatment. METHODS: Full-thickness scalp biopsies were sampled from healthy volunteers and those with dandruff. Immunohistochemistry for Ki67 and keratin 16 was used to examine keratinocyte proliferation and differentiation. Mass spectrometry lipidomics was applied to profile scalp skin barrier lipids and lipid mediators. The presence of immune cells and their cytokine production was examined by flow cytometry. Cytokine and chemokine levels in scalp skin were analysed by cytometric bead array. RESULTS: Increased keratinocyte proliferation and aberrant keratinocyte differentiation were observed in dandruff relative to healthy scalp; however, this epidermal dysregulation was not mirrored by alterations to barrier lipid levels. Decreased numbers of innate lymphoid cells and reduced expression of CD86 on antigen-presenting cells, were the few cellular alterations observed in dandruff scalp, suggesting dandruff only subtly changes major skin immune cell populations. Despite this, increased proportions of interleukin-17-producing T-cells and increased C-C Motif Chemokine Ligand 17 (CCL17) levels were observed in dandruff scalp, indicative of a low-grade, mixed Type-2/Type17 inflammatory response. Increased levels of N-acyl ethanolamines, including the endocannabinoid anandamide, as well as linoleoyl- and oleoyl-ethanolamine, were also observed in dandruff scalp which could be responsible for suppressing inflammation to sub-clinical levels. CONCLUSION: These findings indicate that, contrary to being a mere flaking disorder, dandruff involves an altered inflammatory environment consistent with low-grade inflammation.