Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Multi-Modal Single-Cell Sequencing Identifies Cellular Immunophenotypes Associated With Juvenile Dermatomyositis Disease Activity.


Juvenile dermatomyositis (JDM) is a rare autoimmune condition with insufficient biomarkers and treatments, in part, due to incomplete knowledge of the cell types mediating disease. We investigated immunophenotypes and cell-specific genes associated with disease activity using multiplexed RNA and protein single-cell sequencing applied to PBMCs from 4 treatment-naive JDM (TN-JDM) subjects at baseline, 2, 4, and 6 months post-treatment and 4 subjects with inactive disease on treatment. Analysis of 55,564 cells revealed separate clustering of TN-JDM cells within monocyte, NK, CD8+ effector T and naive B populations. The proportion of CD16+ monocytes was reduced in TN-JDM, and naive B cells and CD4+ Tregs were expanded. Cell-type differential gene expression analysis and hierarchical clustering identified a pan-cell-type IFN gene signature over-expressed in TN-JDM in all cell types and correlated with disease activity most strongly in cytotoxic cell types. TN-JDM CD16+ monocytes expressed the highest IFN gene score and were highly skewed toward an inflammatory and antigen-presenting phenotype at both the transcriptomic and proteomic levels. A transitional B cell population with a distinct transcriptomic signature was expanded in TN-JDM and characterized by higher CD24 and CD5 proteins and less CD39, an immunoregulatory protein. This data provides new insights into JDM immune dysregulation at cellular resolution and serves as a novel resource for myositis investigators.

Authors: Neely J, Hartoularos G, Bunis D, Sun Y, Lee D, Kim S, Ye CJ, Sirota M,
Journal: Front Immunol;2022; 13 902232. doi:10.3389/fimmu.2022.902232
Year: 2022
PubMed: PMID: 35799782 (Go to PubMed)