RATIONALE: The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. OBJECTIVES: We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. METHODS: CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1-4) by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3-4 (P < 0.01 for GOLD 3-4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV(1) (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. CONCLUSIONS: These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells.
RATIONALE: The mechanisms underlying formation of lung lymphoid follicles (LF) in chronic obstructive pulmonary disease (COPD) are unknown. The chemokine receptor CXCR3 regulates immune responses in secondary lymphoid structures elsewhere in the body and is highly expressed by Th1 lymphocytes in the airway in COPD. Because chemokine receptors control inflammatory cell homing to inflamed tissue, we reasoned that CXCR3 may contribute to LF formation in COPD. OBJECTIVES: We assessed the expression of CXCR3 and its ligands (IP-10/CXCL10, Mig/CXCL9, and ITAC/CXCL11) by LF cells in never-smokers, smokers without COPD, and subjects with COPD. METHODS:CXCR3, IP-10, Mig, and ITAC expression were assessed in lung sections from 46 subjects (never-smokers, smokers without COPD [S], and subjects with COPD in GOLD stages 1-4) by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS:CXCR3-expressing T cells (CD8+ or CD4+) and B cells (CD20+) were topographically distributed at the follicle periphery and center, respectively. The percentage of immunohistochemically identified CXCR3+ cells increased progressively while proceeding from S through GOLD 3-4 (P < 0.01 for GOLD 3-4 vs. S). Moreover, the number of CXCR3+ follicular cells correlated inversely with FEV(1) (r = 0.60). The CXCR3 ligands IP-10 and Mig were expressed by several cell types in and around the follicle, including CD68+ dendritic cells/ macrophages, airway epithelial cells, endothelial cells, and T and B cells. CONCLUSIONS: These results suggest that LF form in the COPD lung by recruitment and/or retention of CXCR3-expressing T and B lymphocytes, which are attracted to the region through production of CXCR3 ligands IP-10 and Mig by lung structural and follicular cells.
Authors: Laimute Taraseviciene-Stewart; Nana Burns; Donatas Kraskauskas; Mark R Nicolls; Rubin M Tuder; Norbert F Voelkel Journal: Proc Am Thorac Soc Date: 2006-08
Authors: Claudia Costa; Rogerio Rufino; Suzanne L Traves; Jose Roberto Lapa E Silva; Peter J Barnes; Louise E Donnelly Journal: Chest Date: 2007-10-09 Impact factor: 9.410
Authors: F Sallusto; E Kremmer; B Palermo; A Hoy; P Ponath; S Qin; R Förster; M Lipp; A Lanzavecchia Journal: Eur J Immunol Date: 1999-06 Impact factor: 5.532
Authors: Elizabeth L Hardaker; Alicia M Bacon; Karey Carlson; Amy K Roshak; James J Foley; Dulcie B Schmidt; Peter T Buckley; Meghan Comegys; Reynold A Panettieri; Henry M Sarau; Kristen E Belmonte Journal: FASEB J Date: 2003-11-03 Impact factor: 5.191
Authors: Gerhard C Hildebrandt; Leigh A Corrion; Krystyna M Olkiewicz; Bao Lu; Kathleen Lowler; Ulrich A Duffner; Bethany B Moore; William A Kuziel; Chen Liu; Kenneth R Cooke Journal: J Immunol Date: 2004-08-01 Impact factor: 5.422
Authors: Amit A Lugade; R Robert Vethanayagam; Mehrab Nasirikenari; Paul N Bogner; Brahm H Segal; Yasmin Thanavala Journal: Am J Respir Cell Mol Biol Date: 2011-01-07 Impact factor: 6.914
Authors: Chuang Xu; Sean Hesselbacher; Chu-Lin Tsai; Ming Shan; Margaret Spitz; Michael Scheurer; Luz Roberts; Sarah Perusich; Nazanin Zarinkamar; Harvey Coxson; Natasha Krowchuk; David B Corry; Farrah Kheradmand Journal: Front Immunol Date: 2012-08-27 Impact factor: 7.561