Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer

Liu, Jared; Chang, Hsin-Wen; Huang, Zhiming; Nakamura, Mio; Sekhon, Sahil; Ahn, Richard; Muñoz-Sandoval, Priscila; Bhattarai, Shrishti; Beck, Kristen M.; Sanchez, Isabelle M.; Yang, Eric J.; Pauli, Mariela; Arron, Sarah T.; Fung‐Leung, Wai‐Ping; Munoz, Ernesto; Liu, Xuejun; Bhutani, Tina; North, Jeffrey P.; Fourie, Anne M.; Rosenblum, Michael D.; Liao, Wilson

doi:10.1016/j.jaci.2020.11.028

Cited by 101 publications

(102 citation statements)

References 58 publications

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“…The imiquimod-driven inflammation model we employed mimics many features of psoriasis at the histological and transcriptional levels [17,18]. Many studies, based on both mouse models and psoriasis patient samples, have illustrated alterations in whole skin, keratinocytes, resident lymphoid cells, macrophages, and other cell types, while changes in the LECs lining the draining LNs have not been studied before [56][57][58]. It is worth noting that many LN LEC-subtype markers remained differentially expressed in their respective locations upon inflammation, indicating that the general distinction between LEC subsets is maintained.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Sibler

Ducoli

et al. 2021

Cells

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The lymphatic system plays a crucial role in immunity and lymph nodes (LNs) undergo drastic remodeling during inflammation. Here, we used single-cell RNA sequencing to investigate transcriptional changes in lymphatic endothelial cells (LECs) in LNs draining naïve and inflamed skin. We found that subsets of LECs lining the different LN sinuses responded individually to skin inflammation, suggesting that they exert distinct functions under pathological conditions. Among the genes dysregulated during inflammation, we confirmed an up-regulation of CD200 in the LECs lining the subcapsular sinus floor with a possible function in immune regulation. Furthermore, by in silico analysis, we predicted numerous possible interactions of LECs with diverse immune cells in the LNs and found similarities in the transcriptional changes of LN LECs in different skin inflammation settings. In summary, we provide an in-depth analysis of the transcriptional landscape of LN LECs in the naïve state and in skin inflammation.

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Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Sibler

Ducoli

et al. 2021

Cells

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“…The traditional cytotoxic role of CD8+ T cells may also be associated with psoriasis pathology, as CD8+ T cells that produce the cytotoxic mediator granulysin outnumber CD8+ T cells that do not in the blood and skin of psoriasis patients [ 141 ]. There are 11 subtypes of CD8+ T cells in the skin when analysed by RNA profile [ 142 ]. The two subclasses most uniquely found in psoriatic lesions produce IL-17, named Tc17 cells [ 142 ].…”

Section: Barrier Aberration In Psoriasismentioning

confidence: 99%

“…There are 11 subtypes of CD8+ T cells in the skin when analysed by RNA profile [ 142 ]. The two subclasses most uniquely found in psoriatic lesions produce IL-17, named Tc17 cells [ 142 ]. The prevalence of Tc17 cells in psoriatic lesions correlates with disease duration, further evidencing their importance [ 143 ].…”

Section: Barrier Aberration In Psoriasismentioning

confidence: 99%

Skin Barrier Dysregulation in Psoriasis

Andreas

Bereza-Malcolm

Lynch

et al. 2021

IJMS

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The skin barrier is broadly composed of two elements—a physical barrier mostly localised in the epidermis, and an immune barrier localised in both the dermis and epidermis. These two systems interact cooperatively to maintain skin homeostasis and overall human health. However, if dysregulated, several skin diseases may arise. Psoriasis is one of the most prevalent skin diseases associated with disrupted barrier function. It is characterised by the formation of psoriatic lesions, the aberrant differentiation and proliferation of keratinocytes, and excessive inflammation. In this review, we summarize recent discoveries in disease pathogenesis, including the contribution of keratinocytes, immune cells, genetic and environmental factors, and how they advance current and future treatments.

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“…In conclusion, understanding skin fibroblast heterogeneity is of great relevance not only in homeostasis, but also in ageing 11,29 and disease. [30][31][32][33][34] Further refinement of fibroblasts subsets and their identity-defining features will provide a fruitful framework for the advancement of knowledge as well as for the development of novel therapeutic approaches in dermatological disease and skin cancer.…”

Section: Discussionmentioning

confidence: 99%

The need to reassess single-cell RNA sequencing datasets: more is not always better

2021

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Background: The advent of single-cell RNA sequencing (scRNAseq) and additional single-cell omics technologies have provided scientists with unprecedented tools to explore biology at cellular resolution. However, reaching an appropriate number of good quality reads per cell and reasonable numbers of cells within each of the populations of interest are key to infer conclusions from otherwise limited analyses. For these reasons, scRNAseq studies are constantly increasing the number of cells analysed and the granularity of the resultant transcriptomics analyses. Methods: We aimed to identify previously described fibroblast subpopulations in healthy adult human skin by using the largest dataset published to date (528,253 sequenced cells) and an unsupervised population-matching algorithm. Results: Our reanalysis of this landmark resource demonstrates that a substantial proportion of cell transcriptomic signatures may be biased by cellular stress and response to hypoxic conditions. Conclusions: We postulate that the ”more is better” approach, currently prevalent in the scientific community, might undermine the extent of the analysis, possibly due to long computational processing times inherent to large datasets.

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Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer

Cited by 101 publications

References 58 publications

Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes

Skin Barrier Dysregulation in Psoriasis

The need to reassess single-cell RNA sequencing datasets: more is not always better

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