Lymphoid Follicle Cells in Chronic Obstructive Pulmonary Disease Overexpress the Chemokine Receptor CXCR3

• Published in: American journal of respiratory and critical care medicine Vol. 179; no. 9; pp. 799 - 805
• Main Authors: Kelsen, Steven G, Aksoy, Mark O, Georgy, Mary, Hershman, Richard, Ji, Rong, Li, XiuXia, Hurford, Matthew, Solomides, Charalambos, Chatila, Wissam, Kim, Victor
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01-05-2009; American Thoracic Society
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens; B-Lymphocytes - cytology; B-Lymphocytes - metabolism; B. Chronic Obstructive Pulmonary Disease; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Case-Control Studies; Chemokine CXCL10 - metabolism; Chemokine CXCL9 - metabolism; Chemokines; Chronic obstructive pulmonary disease; Dendritic cells; Female; Follicles; Forced Expiratory Volume; Humans; Immunohistochemistry; Intensive care medicine; Ligands; Lung - metabolism; Lung diseases; Lungs; Lymphocytes; Lymphoid Tissue - cytology; Lymphoid Tissue - metabolism; Male; Medical sciences; Middle Aged; Ostomy; Pulmonary arteries; Pulmonary Disease, Chronic Obstructive - metabolism; Receptors, CXCR3 - metabolism; Smoking - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplants & implants; Lung disease; Lymphoid cell; Intensive care; Respiratory disease; Inflammation; Chemokine receptor; chemokines; Chemokine; cell recruitment; Bronchus disease; Chronic obstructive pulmonary disease; Resuscitation; lung inflammation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200807-1089OC

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.
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.
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.
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.
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.