Lymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.

TitleLymphoid follicle cells in chronic obstructive pulmonary disease overexpress the chemokine receptor CXCR3.
Publication TypeJournal Article
Year of Publication2009
AuthorsKelsen SG, Aksoy MO, Georgy M, Hershman R, Ji R, Li X, Hurford M, Solomides C, Chatila W, Kim V
JournalAm J Respir Crit Care Med
Date Published2009 May 1
KeywordsB-Lymphocytes, Case-Control Studies, Chemokine CXCL10, Chemokine CXCL9, Female, Forced Expiratory Volume, Humans, Immunohistochemistry, Lung, Lymphoid Tissue, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Receptors, CXCR3, Smoking, T-Lymphocytes

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

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.

Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID19218194