This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200609-1347OCv1 176/10/1007    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marchal-Sommé, J. Articles by Soler, P. Search for Related Content PubMed PubMed Citation Articles by Marchal-Sommé, J. Articles by Soler, P.

Dendritic Cells Accumulate in Human Fibrotic Interstitial Lung Disease

¹ Inserm, U 700, and Faculté de Médecine Paris-Nord, site Bichat, Université Paris 7, Paris, France; ² Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; and ³ Service d'Anatomo-Pathologie and ⁴ Service de Pneumologie, Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France

Correspondence and requests for reprints should be addressed to Paul Soler, Ph.D., Inserm U700, Faculté de Medicine Paris-Nord, site Bichat, 16 rue Henri Huchard, 75018 Paris, France. E-mail: soler{at}bichat.inserm.fr

Rationale: 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.

Objectives: 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.

Measurements and Main 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.

Key Words: chronic inflammation • dendritic cells • epithelial cells • fibroblasts • idiopathic pulmonary fibrosis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Dendritic cells are potent antigen-presenting cells able to sustain chronic inflammation. However, current information about the distribution of dendritic cells in idiopathic pulmonary fibrosis lung is lacking. What This Study Adds to the Field Dendritic cells with the potential to sustain chronic inflammation infiltrate the idiopathic pulmonary fibrosis lung. Hyperplastic epithelial cells and fibroblasts could play a key role by driving the accumulation of dendritic cells into the lungs during pulmonary fibrosis.

 

This article has been cited by other articles:

				A. U. Wells and C. M. Hogaboam Update in Diffuse Parenchymal Lung Disease 2007 Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 580 - 584. [Full Text] [PDF]