Analysis of the Pathogenesis of Secondary Airflow Limitation in Tuberculosis based on ILC3 Chemotaxis

Introduction Tuberculosis-associated obstructive pulmonary disease (TOPD) remains poorly understood; accumulating evidence implicates innate lymphoid cells (ILCs), especially group 3 (ILC3), in post-tuberculous airway remodelling. We aimed to clarify whether CXCL13-CXCR5–directed ILC3 chemotaxis contributes to secondary airflow limitation. Methods In a case-control study, 34 patients with TOPD, 34 with stable chronic obstructive pulmonary disease (COPD) unrelated to tuberculosis, and 34 healthy controls were recruited. Peripheral blood and broncho-alveolar lavage fluid (BALF) were collected within 24 h of enrolment. Total ILCs and subsets were quantified using multiparameter flow cytometry; ELISA was used to measure CXCL13, CXCR5, IFN-γ, IL-23, IL-17, and IL-22. Group differences were analysed with one-way ANOVA or the Friedman test (p < 0.05). Results Circulating ILC3 frequency was reduced in TOPD versus COPD and controls (p < 0.001). Conversely, the BALF ILC3 proportion was markedly higher in TOPD than in COPD and control subjects (p < 0.001). TOPD patients exhibited the greatest systemic elevation of CXCL13, IL-23, IL-17, and IL-22 (all p < 0.01) and the highest BALF levels of CXCL13, CXCR5, and the same cytokines (all p < 0.001). IFN-γ levels and BALF ILC1 counts were also elevated, whereas changes in ILC2 were restricted to peripheral blood. Discussion The reciprocal pattern of diminished peripheral yet enriched pulmonary ILC3, together with a CXCL13-CXCR5 gradient, supports the selective recruitment of ILC3 from blood to lung parenchyma following Mycobacterium tuberculosis infection, sustaining type 3 inflammation beyond microbiological cure. Although the cross-sectional design and modest sample size limit causal inference, the findings align with experimental models and extend knowledge to human TOPD. Conclusion TOPD is characterized by CXCL13-CXCR5–mediated trafficking of ILC3 that amplifies IL-23/IL-17/IL-22–driven airway inflammation, indicating this chemokine axis as a promising biomarker and therapeutic target for post-tuberculous airflow obstruction and progressive pulmonary decline.