Leveraging blood and tissue CD4+ T cell heterogeneity at the single cell level to identify mechanisms of disease in rheumatoid arthritis

- Single cell immunoprofiling reveals extensive heterogeneity among CD4+ T cells.
- Multidimensional analyses identify novel CD4+ T cell populations associated with rheumatoid arthritis.
- Single cell disease association studies require careful attention to study design to avoid confounding technical effects.
- New analysis methods are emerging to take full advantage of complex single cell datasets.

CD4+ T cells have been long known to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the specific cell populations and states that drive the disease have been challenging to identify with low dimensional single cell data and bulk assays. The advent of high dimensional single cell technologies - like single cell RNA-seq or mass cytometry - has offered promise to defining key populations, but brings new methodological and statistical challenges. Recent single cell profiling studies have revealed a broad diversity of cell types among CD4+ T cells, identifying novel populations that are expanded or altered in RA. Here, we will review recent findings on CD4+ T cell heterogeneity and RA that have come from single cell profiling studies and discuss the best practices for conducting these studies.