Single‐cell profiles reveal distinctive immune response in atopic dermatitis in contrast to psoriasis

Abstract

Background Understanding the complex orchestrated inflammation in atopic dermatitis (AD), one of the most common chronic inflammatory diseases worldwide, is essential for therapeutic approaches. However, a comparative analysis on the single‐cell level of the inflammation signatures correlated with the severity is missing so far. Methods We applied single‐cell RNA and T‐cell receptor (TCR) sequencing on immune cells enriched from skin biopsies and matched blood samples of AD in comparison with psoriasis (PS) patients. Results Clonally propagated skin‐derived T cells showed disease‐specific TCR motifs shared between patients which was more pronounced in PS compared to AD. The disease‐specific T‐cell clusters were mostly of a Th2/Th22 sub‐population in AD and Th17/Tc17 in PS, and their numbers were associated with severity scores in both diseases. Herein, we provide for the first time a list that associates cell type‐specific gene expression with the severity of the two most common chronic inflammatory skin diseases. Investigating the cell signatures in the patients´ PBMCs and skin stromal cells, a systemic involvement of type‐3 inflammation was clearly detectable in PS circulating cells, while in AD inflammatory signatures were most pronounced in fibroblasts, pericytes, and keratinocytes. Compositional and functional analyses of myeloid cells revealed the activation of antiviral responses in macrophages in association with disease severity in both diseases. Conclusion Different disease‐driving cell types and subtypes which contribute to the hallmarks of type‐2 and type‐3 inflammatory signatures and are associated with disease activities could be identified by single‐cell RNA‐seq and TCR‐seq in AD and PS.

Spatial transcriptomics combined with single‐cell RNA‐sequencing unravels the complex inflammatory cell network in atopic dermatitis

“…Here, we identified CCL13‐ and CCL18‐expressing M2 subpopulations in the leukocyte‐infiltrated area in LS that show similar distribution with AD‐specific fibroblasts, DCs, and T cells. Zhang et al also reported increased expression of CCL13 and CCL18 in the macrophage along with AD severity 27 Rapamycin, which is a macrolide compound, downregulates the release of CCL13 and CCL18 from IL‐4‐treated macrophages and inhibits Dermatophagoides farinae body antigen‐induced dermatitis in NC/Nga mice 51 . M2 macrophages may represent a potential target for the mTOR inhibitors; rapamycin, cyclosporine, and tacrolimus.…”

“…Several recent studies have demonstrated the complex inflammatory characteristics of the AD skin. [22][23][24][25][26] In addition, recently reported single-cell RNA-seq analyses provided a wealth of information on skin-infiltrating cell subsets and demonstrate the clear difference between AD and psoriasis, 27,28 but there was a lack of information on spatial and neighboring cells, particularly in the leukocyte infiltrating area. 9,10,29,30 Spatial transcriptomics enables us to molecularly characterize transcriptomes of the specific localizations.…”

Antigen-specificity measurements are the key to understanding T cell responses

“…One study examined patients with psoriatic arthritis to show predominantly CD8+ clonal expansions in the joint fluid, pointing to a critical role for these cells in disease (158). Another study examined skin inflammatory diseases, finding differences in the transcriptional signatures and clonal expansion of T cells in psoriasis versus atopic dermatitis (159). A third study showed clonal expansion of activated, cytotoxic T cells in cerebrospinal fluid in patients with multiple sclerosis (MS) (160).…”

The extrinsic factors important to the homeostasis of allergen-specific memory CD4 T cells

“…The level of this gene was highly expressed in the lung CD4 T RM cells than in circulating memory CD4 T cells after allergic lung inflammation ( 17 ). Moreover, recent research reported that the CXCR6 expression on Th2 cells correlated with the severity of atopic dermatitis ( 66 ).…”