Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease.
Tingting LiuZhen-Zhen WangXiaotong XueZhe WangYuan ZhangZihao MiQing ZhaoLele SunChuan WangPeidian ShiGongqi YuMeng WangYonghu SunFuzhong XueHong LiuFuren ZhangPublished in: Nature communications (2024)
Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand-receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.
Keyphrases
- single cell
- rna seq
- bone marrow
- induced apoptosis
- dendritic cells
- high throughput
- cell cycle arrest
- oxidative stress
- extracellular matrix
- cell death
- end stage renal disease
- cell proliferation
- signaling pathway
- endoplasmic reticulum stress
- immune response
- newly diagnosed
- risk assessment
- acute myeloid leukemia
- dna methylation
- liver fibrosis
- cell therapy
- stem cells
- systemic lupus erythematosus
- patient reported outcomes
- gene expression
- human health
- current status
- patient reported