T-cell Multiomic Analysis Identifies Subsets and Mechanisms of Interaction with Epithelial Cells in Idiopathic Pulmonary Fibrosis

While T-cell numbers are elevated in IPF lungs, including in fibrotic regions, their contributions to fibrosis, especially beyond inflammation, remain unclear. We used single-cell RNA and protein profiling (CITE-seq) of CD3⁺ T cells from control and fibrotic lungs to investigate molecular pathways involved in T-cell functions in pulmonary fibrosis. This study reveals a previously unrecognized role for MIF/CXCR4/EGFR signaling in T-cell activation. Targeting the epithelial–T-cell axis may provide novel therapeutic strategies to mitigate T-cell-mediated epithelial damage and slow IPF progression.