A role for dendritic cells in bleomycin-induced pulmonary fibrosis in mice?
BACKGROUND
Lung dendritic cells (DCs) have been shown to accumulate in human fibrotic lung disease, but little is known concerning a role for DCs in the pathogenesis of fibrotic lung.


OBJECTIVE
To characterize lung DCs in an in vivo model of bleomycin-induced pulmonary fibrosis in mice.


METHODS
We characterized the kinetics and activation of pulmonary DCs during the course of bleomycin-induced lung injury by flow cytometry on lung single-cell suspensions. We also characterized the lymphocytes accumulating in bleomycin lung and the chemokines susceptible to favor the recruitment of immune cells.


RESULTS
We show, for the first time, that increased numbers of CD11c(+)/major histocompatibility complex class II(+) DCs, including CD11b(hi) monocyte-derived inflammatory DCs, infiltrate the lung of treated animals during the fibrotic phase of the response to bleomycin. These DCs are mature DCs expressing CD40, CD86, and CD83. They are associated with increased numbers of recently activated memory T cells expressing CD44, CD40L, and CD28, suggesting that fully mature DCs and Ag-experienced T cells can drive an efficient effector immune response within bleomycin lung. Most importantly, when DCs are inactivated with VAG539, a recently described new immunomodulator, VAG539 treatment attenuates the hallmarks of bleomycin lung injury.


CONCLUSIONS
These findings identify lung DCs as key proinflammatory cells potentially able to sustain pulmonary inflammation and fibrosis in the bleomycin model.
Bantsimba-Malanda
Claudie
C
INSERM U700, Université Paris Diderot-Paris 7, UFR de Médecine-site Bichat, France.
Marchal-Sommé
Joëlle
J
Goven
Delphine
D
Freynet
Olivia
O
Michel
Laurence
L
Crestani
Bruno
B
Soler
Paul
P
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008285:Major Histocompatibility Complex / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism
D015703:Antigens, CD; D018925:Chemokines; D007155:Immunologic Factors; D001761:Bleomycin