Stromal-like Cells Are Found in Peripheral Blood of Inflammatory Bowel Disease Patients and Correlate with Immune Activation State

Clin Transl Gastroenterol. 2024 Jun 1. doi: 10.14309/ctg.0000000000000721. Online ahead of print.


Introduction: Recent studies have identified a critical role for stromal-immune cell interactions in immunity and immune tolerance. Transcriptomic profiling has implicated stromal cells in immune-mediated disorders including the two common forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). Stromal-immune interactions may edify inflammatory state and the development of IBD-related complications such as fibrosis; yet the lack of protein markers has hampered studying stromal-immune perturbation.

Methods: In this study, we designed a 40-color spectral flow cytometry assay to characterize hematopoietic and nonhematopoietic cells in intestinal biopsies and matched blood samples from patients with CD or UC.

Results: We identified circulating stromal-like cells that are significantly more abundant in IBD blood samples than in healthy controls. Those cells expressed podoplanin (PDPN), a commonly used marker for fibroblasts, and they were associated with activated and memory T and B cells, and altered NK cell, monocyte, and macrophage populations. PDPN+ cells in the blood correlated with PDPN+ cells in the colon. Principal component analysis distinctly separated healthy blood samples from IBD blood samples, with stromal-like cells and B cell subtypes dominating the IBD signature; Pearson correlation detected an association between PDPN+ stromal-like cells and B cell populations in IBD blood and gut biopsies.

Discussion: These observations suggest that PDPN+ cells in the blood may serve as a biomarker of IBD. Understanding the relationship between stromal cells and immune cells in the intestine and the blood may provide a window into disease pathogenesis and insight into therapeutic targets for IBD.