Crohn's disease under single-cell map: from INFLARE metaplastic cells to rare immune cell subpopulations

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract characterized by symptoms such as abdominal pain, diarrhea, weight loss, fever, and fatigue. Although the exact etiology of CD remains elusive, dysregulation of immune cells is widely recognized as a primary driver in its pathogenesis, particularly involving T helper 1 (Th1), T helper 17 (Th17), and natural killer T (NKT) cells. Recent advancements in single-cell sequencing technology have provided a powerful tool for analyzing gene expression at the individual cell level, enabling researchers to investigate immune cells within the microenvironment of disease samples with unprecedented resolution. Through the application of this technology, several novel and unique immune cell subsets have been identified in Crohn's disease, which are critical to its development and progression. This review summarizes these CD-associated cell types, including INFLAREs, LND cells, Tc1/17 cells, tissue-resident memory (Trm) CD8⁺ T cells, FOXP3⁺ regulatory T cells (Tregs), CD pop cells, α⁴β⁷⁺CLA⁺ T cells, NKp30⁺ γδ T cells, and Crohn's disease-associated invariant T cells (CAITs). We discuss their specific roles in the pathogenesis of CD and explore their potential as targets for the development of future therapeutic interventions. Thereby, this may serve as a conceptual and practical resource​ for researchers and clinicians seeking to understand the immunological intricacies of CD and translate them into improved patient outcomes in the future.