Role of lymphotoxin-alpha in cigarette smoke-induced inflammation and lymphoid neogenesis
(2009) The European Respiratory Journal — Vol. 34, n° 2, p. 405-416 (2009)
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- In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-alpha, crucial in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis. We examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and inflammation in vivo in LT alpha knockout (LT alpha(-/-)) and wild-type (WT) mice and studied the expression of lymphoid chemokines by lung fibroblasts in vitro. T-cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid aggregate numbers were significantly higher in air-exposed LT alpha(-/-) mice than in WT animals, and increased upon chronic CS exposure in both genotypes. In contrast, local immunoglobulin A responses upon chronic CS exposure were attenuated in LT alpha(-/-) mice. CXC chemokine ligand (CXCL) 13 and CC chemokine ligand (CCL) 19 mRNA in total lung and CXCL13 protein level in BALF increased upon CS exposure in WT, but not in LT alpha(-/-) mice. In vitro lymphotoxin-beta receptor (LT beta R) stimulation induced CXCL13 and CCL19 mRNA in WT lung fibroblasts. Furthermore, in vitro exposure to CS extract upregulated CXCL13 mRNA expression in WT, but not in LT beta R-/-, lung fibroblasts. In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LT alpha beta-LT beta R-dependent fashion. However, LT alpha is not required for CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates.
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Demoor, T., Bracke, K. R., Maes, T., Vandooren, B., Elewaut, D., Pilette, C., Joos, G. F., & Brusselle, G. G. (2009). Role of lymphotoxin-alpha in cigarette smoke-induced inflammation and lymphoid neogenesis. The European Respiratory Journal, 34(2), 405-416. https://doi.org/10.1183/09031936.00101408 (Original work published 2009)