TY - JOUR T1 - Role of lymphotoxin-α in cigarette smoke-induced inflammation and lymphoid neogenesis JF - European Respiratory Journal JO - Eur Respir J SP - 405 LP - 416 DO - 10.1183/09031936.00101408 VL - 34 IS - 2 AU - T. Demoor AU - K. R. Bracke AU - T. Maes AU - B. Vandooren AU - D. Elewaut AU - C. Pilette AU - G. F. Joos AU - G. G. Brusselle Y1 - 2009/08/01 UR - http://erj.ersjournals.com/content/34/2/405.abstract N2 - In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-α, 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 LTα knockout (LTα-/-) 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 LTα-/- 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 LTα-/- 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 LTα-/- mice. In vitro lymphotoxin-β receptor (LTβR) 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 LTβR-/-, lung fibroblasts. In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LTαβ–LTβR-dependent fashion. However, LTα is not required for CS-induced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates. ER -