Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Single-cell profiling of peripheral blood and muscle cells reveals inflammatory features of juvenile dermatomyositis.


Introduction: Juvenile dermatomyositis (JDM) is a rare yet serious childhood systemic autoimmune condition that primarily causes skin rashes and inflammatory myopathy of the proximal muscles. Although the associated immune response involves the innate and adaptive arms, a detailed analysis of the pertinent immune cells remains to be performed. This study aims to investigate the dynamic changes of cell type, cell composition and transcriptional profiles in peripheral blood and muscle tissues, and in order to clarify the involvement of immune cells in the pathogenesis of JDM and provide a theoretical reference for JDM. Methods: Single-cell RNA sequencing combined with bioinformatic analyses were used to investigate the dynamic changes in cell composition and transcriptional profiles. Results: Analysis of 45,859 cells revealed nine and seven distinct cell subsets in the peripheral blood and muscle tissues respectively. IFITM2+ and CYP4F3+ monocytes were largely produced, and CD74+ smooth muscle cells (SMCs) and CCL19+ fibroblasts were identified as inflammatory-related cell subtypes in JDM patients, exhibiting patient-specific cell population heterogeneity.The dynamic gene expression patterns presented an enhanced type I interferon response in peripheral blood monocytes and T-cells, and SMCs and fibroblasts in muscle of untreated JDM patients. EGR1 and IRF7 may play central roles in the inflammation in both CD74+ SMCs and CCL19+ fibroblasts. Moreover, inflammatory-related monocytes could regulate T-cells, and the interaction between immune cells and SMCs or fibroblasts in muscle was enhanced under the inflammatory state. Conclusions: Immune dysregulation is one of the key pathogenic factors of JDM, and type I interferon responses are significantly enhanced in peripheral blood Monos and T cells as well as SMCs and fibroblasts. EGR1 and IRF7 may play central roles in the inflammation and are considered as potential therapeutic targets for JDM.

Authors: Chen X, Lian D, Zeng H.
Journal: Front Cell Dev Biol . 2023 Apr 20;11:1166017. doi: 10.3389/fcell.2023.1166017. eCollection 2023.
Year: 2023
PubMed: PMID: 37152289 (Go to PubMed)