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


OBJECTIVE
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.


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.
Kelsen
Steven G
SG
761 Parkinson Pavilion, Temple University Hospital, 3401 N. Broad St., Philadelphia, PA 19140, USA. kelsen@temple.edu
Aksoy
Mark O
MO
Georgy
Mary
M
Hershman
Richard
R
Ji
Rong
R
Li
Xiuxia
X
Hurford
Matthew
M
Solomides
Charalambos
C
Chatila
Wissam
W
Kim
Victor
V
D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3