Activated immune cells present a lung interstitial-to-airway/alveolar cross-compartment sharing pattern in severe pneumonia

Abstract

Background: Immune cells play a pivotal role in the pathogenesis of severe pneumonia. However, the global atlas of immune cells under this condition is not fully understood.

Methods: We conducted single-cell analyses of 275 411 cells isolated from matched lung tissue, bronchoalveolar lavage fluid, and peripheral blood from 12 patients with severe pneumonia and 5 donors, in order to identify the cross-compartment sharing pattern of activated immune cells and the roles they play in severe pneumonia.

Results: Our observations revealed that activated immune cells distributed across lung interstitia and airways (alveoli; Pattern 1a), including activated tissue-resident memory-like CD8⁺ T cells (T8_rms), plasma cells and plasmablasts, and the pro-inflammatory macrophages. The activated T8_rms were derived from circulating CX3CR1⁺ CD8⁺ T cells, which upregulated ITGAE and CXCR3 during lung infiltration. Similarly, plasma cells and plasmablasts expressing ITGAE and CXCR3 also indicated the potential lung interstitial-to-airway/alveolar sharing pattern. The pro-inflammatory macrophages interacted with T8_rms and plasma cells via the CXCL10-CXCR3 axis.

Conclusions: The lung interstitial-to-airway/alveolar cross-compartment sharing pattern of activated immune cells (Pattern 1a) provide a robust working hypothesis for clinical and translational research for severe pneumonia.

Keywords

immune cells / immunology / severe pneumonia / single-cell sequencing

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2026 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.