Spatial Single-Cell Profiling of the Mucosal Immune Microenvironment Across Varied Respiratory Volumes in Patients with Refractory Chronic Cough

Original Research | 2026 | Volume 1 | Issue 1 | Page 08-14

1. Dr. Sumit Kumar Vishwakarma, Associate Professor, Department of General Medicine, Ramkrishna Medical College, Bhopal

2. Dr. Shahan Layek, Independent Researcher, West Bengal, India

3. Dr. Manoj Kumar, Tutor, Department of Physiology, JHMC, WB

Spatial Single-Cell Profiling of the Mucosal Immune Microenvironment Across Varied Respira.

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Corresponding Author:-

Dr. Manoj Kumar

Tutor, Department of Physiology

JHMC, WB

ABSTRACT

BACKGROUND: Refractory chronic cough (RCC) is characterized by persistent airway hypersensitivity, yet the spatial distribution of immune cells within the mucosal microenvironment remains poorly understood. Variations in respiratory volumes and mechanical strain are hypothesized to modulate local immune signaling, contributing to the cough reflex hypersensitivity. This study employs spatial single-cell profiling to map the mucosal immune microenvironment in RCC patients and assess how these cellular landscapes correlate with localized respiratory mechanics.

METHODS: Endobronchial mucosal biopsies were collected from patients with refractory chronic cough and healthy controls. Spatial transcriptomics and high-dimensional single-cell imaging were utilized to characterize the distribution of immune cell populations, including resident macrophages, T-cell subsets, and sensory nerve-associated immune cells. These spatial data were integrated with pulmonary function testing and dynamic respiratory volume analysis to correlate cellular positioning with varying regional lung volumes.

RESULTS: The spatial profiling revealed a distinct "immune-sensory hub" architecture in RCC patients, characterized by a heightened density of activated T-cells and pro-inflammatory macrophages in close proximity to airway sensory nerve endings. This spatial coupling was significantly more pronounced in lung regions subjected to reduced respiratory excursions, suggesting that altered mechanics may trap inflammatory mediators in specific mucosal niches. Furthermore, sub-epithelial immune cell clustering was associated with an upregulation of neurotrophic factors, correlating directly with the severity of the cough reflex.

CONCLUSION: This study provides a high-resolution map of the mucosal immune microenvironment in refractory chronic cough, identifying spatial hotspots where immune cells and sensory nerves converge. The findings suggest that RCC is not merely a systemic inflammatory disorder but a localized, spatially organized pathology exacerbated by mechanical variations in respiratory volume. These spatial insights highlight potential sites for targeted intervention to disrupt the immune-sensory crosstalk driving cough hypersensitivity.

KEYWORDS: Chronic Cough, Spatial Transcriptomics, Mucosal Immunity, Single-Cell Profiling, Airway Neurobiology, Respiratory Mechanics.