Immune cells in psoriasis skin differ dramatically from blood, opening new treatment targets
Researchers have identified a previously unknown type of neutrophil that appears in psoriasis lesions triggered by strep throat, suggesting the immune response to infection may directly drive skin disease. The finding could reshape how companies develop therapies and help clinicians predict which patients will develop the condition after infection.
Originaltitel: High-dimensional single-cell analyses reveal neutrophil heterogeneity in guttate psoriasis
<h2>Summary</h2><h3>Background</h3> Guttate psoriasis (GP) is associated with streptococcal throat infection. Neutrophils are the first immune cells to respond to Group A Streptococcal (GAS) infection, but detailed analysis of their contribution to GP pathogenesis is lacking. The study primarily focuses on phenotyping the neutrophils located at the site of inflammation in GP skin and understanding their specific contribution to the pathogenesis of the disease. <h3>Methods</h3> Here, we performed a comprehensive immunophenotypic and transcriptomic analysis of neutrophils from blood and inflamed GP skin using high-dimensional single-cell protein and RNA analyses. <i>Ex vivo</i> stimulation of neutrophils and co-culture with CD4<sup>+</sup> T cells was performed to validate the function of neutrophil subsets upon GAS stimulation. <h3>Findings</h3> We uncovered high diversity of human neutrophils in GP, with enrichment of an immature subset in GP skin that exhibited antigen processing and presentation signature. A similar subset in healthy controls was observed only upon <i>ex vivo</i> stimulation of neutrophils with GAS bacteria. Additionally, the GAS-induced neutrophil subset was found to induce CD4<sup>+</sup> T cell proliferation mediated by HLA-DR. Other neutrophil subsets that expanded in GP were characterised by enrichment of genes related to neutrophil migration, formation of neutrophil extracellular traps and phagocytosis. <h3>Interpretation</h3> Our study depicts the landscape of neutrophils in GP skin and highlights HLA-DR<sup>+</sup> neutrophils with possible role in disease pathogenesis. <h3>Funding</h3> This work was supported by HudFonden, Psoriasisfonden, Gösta A Karlssons 60-års fond, Magnus Bergvall stiftelse, Åke Wibergs stiftelse, and Karolinska Institute. AP was supported by HudFonden. PA was partially supported by Karolinska Institute's doctoral funding (KID). LPM was supported by grants from Svenska Sällskapet för Medicinsk Forskning (SSMF) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). UN was supported by grants from the Swedish Research Council. JL was supported by Region Stockholm (clinical postdoctoral appointment). ML was supported by the Swedish Childhood Cancer research fund and the Karolinska Institute. Part of the data handling was enabled by resources at project number SNIC-2021/22-49 provided by the Swedish National Infrastructure for Computing (SNIC), partially funded by the Swedish Research Council through grant agreement no. 2018-05973.