Editorial: "Impact of the Innate and Adaptive Immune System in Driving Type 1 Inflammatory Skin Disease"

Mark Mellett ^1,2* Judit Danis ^3* Barbara Meier-Schiesser ^1,2*

• ¹ University Hospital Zürich, Zurich, Switzerland
• ² University of Zurich, Zürich, Zürich, Switzerland
• ³ University of Szeged, Szeged, Hungary

Type 1 inflammation associated with Th1 cells and Natural Killer cells, is driven primarily by TNFα and IFNγ. These protect against intracellular pathogens and tumour cells but aberrant activation are associated with a myriad of inflammatory skin disorders. While these diseases typically display a type-1 skewed immune bias, this collection of two original research articles, one brief research report, five reviews and one mini-review underscores the roles of both innate and adaptive immune cells in shaping the inflammatory milieu associated with type 1 inflammatory skin diseases. From acne, to eczema, psoriasis and vitiligo, a consistent theme emerges: these diseases are multifactorial processes with a dynamic interplay of multiple cellular and molecular players.Yang et al. provide a comprehensive and timely review on rosacea that exemplifies this complexity of type 1 skin disease. They examine the molecular interactions that drive rosacea pathogenesis, in particular the role of LL37, the human Cathelicidin peptide that displays a wide-range of immunomodulatory functions. In rosacea, LL37 exerts pleiotropic on effector cells -inducing the release of IL-8 from keratinocytes, VEGF from endothelial cells (mediated by mTORC1) and type I Interferons from plasmacytoid dendritic cells (pDCs). IL-8 serves as a chemoattractant of neutrophils and VEGF, in addition to promoting angiogenesis, stimulates Th1 cell differentiation. Through activation of the transient receptor potential vanilloid 4 (TRPV4) LL37 activates macrophages and mast cells. activation and this TLR2-KLK5-LL37-mTOR axis is main therapetuic strategy for disease management. 34Additionally, new treatment strategies, including targeting Th1/Th17 cells, the pathway or the 35 Interestingly, mast cells also play a role in early acne lesions, being recruited by keratinocyte-produced 53 stem cell factor, and are one source of IL-17A at acne lesions. 54These reviews underscore the need for studying the temporal and spatial dynamics of immune activity 55 in acne development, to facilitate more targeted treatments. 56In an original article, Seiringer et al. use spatial transcriptomics to uncover the active role of sebaceous 57 glands in psoriasis vulgaris and atopic dermatitis pathogenesis. Both diseases show altered lipid 58 metabolism in the sebaceous gland transcriptome compared to non-lesional sebaceous glands and the 59 upregulation of inflammatory mediators including serum amyloid A1. In atopic dermatitis, a number of 60 genes associated with lipid skin barrier formation were identified. Interestingly, genes such as ALOX15B, 61 an important regulator of fatty acid metabolism, and CCL17, two of the spatially variable genes 62 upregulated here are known to be induced by type-2 cytokines, IL-4 and IL-13 in macrophages suggests 63 a potential role of sebaceous gland in atopic dermatitis. In psoriatic tissue, sebaceous gland gene 64 expression profiles showed an increase in type I interferon and anti-microbial peptide expression but also heightened differentiation and SUMOylation. These data present sebaceous glands as 66 immunomodulatory structures that contribute to the shaping of the immune environment in skin 67Morelli et al. investigated the difference between anti-PD-1-induced psoriasis in three oncology 69 patients with samples from plaque psoriasis and paradoxical psoriasis (arising from anti-TNFα 70 treatment). Their original research article shows that this immune-related cutaneous adverse event is