# Single-cell transcriptional landscape of peripheral myeloid cells in autoimmune diseases

## TL;DR

This study maps myeloid cell types in autoimmune diseases using single-cell RNA sequencing, revealing distinct subsets and potential drug targets.

## Contribution

The study identifies 13 myeloid subsets and 8 monocyte states, linking them to autoimmune disease mechanisms and drug repurposing opportunities.

## Key findings

- 13 distinct myeloid cell subsets with unique immunological profiles were identified.
- Eight co-expression modules crucial for monocyte function were found to be dysregulated in autoimmune conditions.
- Myeloid subsets were linked to genetic risk factors, showing enrichment in autoimmune disease heritability.

## Abstract

Myeloid cells are pivotal in autoimmune disorder development due to their varied immune response functions yet understanding them at the single-cell level in such conditions is limited. To address this gap, we analyzed 351,905 myeloid cells from 375 single-cell RNA sequencing samples covering 14 autoimmune diseases, which allowed us to classify myeloid cells into 13 distinct subsets with unique immunological profiles. Through pseudotime analysis, we identified a branching process leading to two intermediary inflammatory subtypes and observed dysregulation in eight co-expression modules crucial for monocyte function across autoimmune conditions. Notably, a module linked to myeloid cell activation was consistently upregulated in autoimmune disorders. This insight led us to identify potential drug targets for therapeutic repurposing within the dysregulated modules. By incorporating genetic data from genome-wide association studies, we identified 13 myeloid cell subsets predisposed to varying degrees of risk in different autoimmune conditions.

•Identified 13 functionally distinct myeloid subsets and 8 monocyte cellular states•Revealed cellular states disrupted in autoimmunity and pinpointed drug targets•Myeloid subsets significantly enriched heritability of autoimmune diseases

Identified 13 functionally distinct myeloid subsets and 8 monocyte cellular states

Revealed cellular states disrupted in autoimmunity and pinpointed drug targets

Myeloid subsets significantly enriched heritability of autoimmune diseases

Immunology; Components of the immune system; Transcriptomics