Dendritic cells accumulate in human fibrotic interstitial lung disease.
BACKGROUND
There is growing evidence that resident cells, such as fibroblasts and epithelial cells, can drive the persistent accumulation of dendritic cells (DCs) in chronically inflamed tissue, leading to the organization and the maintenance of ectopic lymphoid aggregates. This phenomenon, occurring through a chemokine-mediated retention mechanism, has been documented in various disorders, but not in fibrotic interstitial lung disorders in which the presence of organized lymphoid follicles has been documented.


OBJECTIVE
To characterize the distribution of DCs in fibrotic lung, and to analyze the expression of the main chemokines known to regulate DC recruitment.


METHODS
Lung resection tissue (lungs with idiopathic pulmonary fibrosis; n = 12; lungs with nonspecific interstitial pneumonia, n = 5; control lungs, n = 5) was snap-frozen for subsequent immunohistochemical techniques on serial sections and reverse transcriptase-polymerase chain reaction analysis.


RESULTS
Results were similar in idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia lungs, which were heavily infiltrated by immature DCs in established fibrosis and in areas of epithelial hyperplasia. Altered epithelial cells and fibroblasts, particularly in fibroblastic foci, frankly expressed all chemokines (CCL19, CCL20, CCL22, and CXCL12) susceptible to favor the recruitment of immune cells. Lymphoid follicles were infiltrated by maturing DCs, which could originate from the pool of DCs accumulating in their vicinity.


CONCLUSIONS
These findings suggest that resident cells in pulmonary fibrosis can sustain chronic inflammation by driving the accumulation of DCs with the potential to mature locally within ectopic lymphoid follicles. Future strategies should consider DCs or chemokines as therapeutic targets in the treatment of pulmonary fibrosis.
Marchal-Sommé
Joëlle
J
Inserm, U 700, and Faculté de Médecine Paris-Nord, site Bichat, Université Paris 7, Paris, France.
Uzunhan
Yurdagul
Y
Marchand-Adam
Sylvain
S
Kambouchner
Marianne
M
Valeyre
Dominique
D
Crestani
Bruno
B
Soler
Paul
P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D019742:Chemokines, CC / Q000378:metabolism*; D003713:Dendritic Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*
D019742:Chemokines, CC