Description:
<jats:sec><jats:title>Objective</jats:title><jats:p>To identify single‐cell transcriptional signatures of dendritic cells (<jats:styled-content style="fixed-case">DC</jats:styled-content>s) that are associated with autoimmunity, and determine whether those <jats:styled-content style="fixed-case">DC</jats:styled-content> signatures are correlated with the clinical heterogeneity of autoimmune disease.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Blood‐derived <jats:styled-content style="fixed-case">DC</jats:styled-content>s were single‐cell sorted from the peripheral blood of patients with rheumatoid arthritis, systemic lupus erythematosus, or type 1 diabetes as well as healthy individuals. <jats:styled-content style="fixed-case">DC</jats:styled-content>s were analyzed using single‐cell gene expression assays, performed immediately after isolation or after in vitro stimulation of the cells. In addition, protein expression was measured using fluorescence‐activated cell sorting.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">CD</jats:styled-content>1c+ conventional <jats:styled-content style="fixed-case">DC</jats:styled-content>s and plasmacytoid <jats:styled-content style="fixed-case">DC</jats:styled-content>s from healthy individuals exhibited diverse transcriptional signatures, while the <jats:styled-content style="fixed-case">DC</jats:styled-content> transcriptional signatures in patients with autoimmune disease were altered. In particular, distinct <jats:styled-content style="fixed-case">DC</jats:styled-content> clusters, characterized by up‐regulation of <jats:italic><jats:styled-content style="fixed-case">TAP</jats:styled-content>1</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">IRF</jats:styled-content>7</jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">IFNAR</jats:styled-content>1</jats:italic>, were abundant in patients with systemic autoimmune disease, whereas <jats:styled-content style="fixed-case">DC</jats:styled-content>s from patients with type 1 diabetes had decreased expression of the regulatory genes <jats:italic><jats:styled-content style="fixed-case">PTPN</jats:styled-content>6</jats:italic>,<jats:italic> <jats:styled-content style="fixed-case">TGFB</jats:styled-content></jats:italic>, and <jats:italic><jats:styled-content style="fixed-case">TYROBP</jats:styled-content></jats:italic>. The frequency of <jats:styled-content style="fixed-case">CD</jats:styled-content>1c+ conventional <jats:styled-content style="fixed-case">DC</jats:styled-content>s that expressed a systemic autoimmune profile directly correlated with the extent of disease activity in patients with rheumatoid arthritis (Spearman's <jats:italic>r</jats:italic> = 0.60, <jats:italic>P</jats:italic> = 0.03).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p><jats:styled-content style="fixed-case">DC</jats:styled-content> transcriptional signatures are altered in patients with autoimmune disease and are associated with the level of disease activity, suggesting that immune cell transcriptional profiling could improve our ability to detect and understand the heterogeneity of these diseases, and could guide treatment choices in patients with a complex autoimmune disease.</jats:p></jats:sec>