An anti-inflammatory role for plasmacytoid dendritic cells in allergic airway inflammation.
It was previously shown that administration of recombinant human Fms-like tyrosine kinase receptor-3 ligand (Flt3L) before allergen challenge of sensitized mice suppresses the cardinal features of asthma through unclear mechanisms. Here, we show that Flt3L dramatically alters the balance of conventional to plasmacytoid dendritic cells (pDCs) in the lung favoring the accumulation of pDCs. Selective removal of pDCs abolished the antiinflammatory effect of Flt3L, suggesting a regulatory role for these cells in ongoing asthmatic inflammation. In support, we found that immature pDCs are recruited to the lungs of allergen-challenged mice irrespective of Flt3L treatment. Selective removal of pDCs during allergen challenge enhanced airway inflammation, whereas adoptive transfer of cultured pDCs before allergen challenge suppressed inflammation. Experiments in which TLR9 agonist CpG motifs were administered in vitro or in vivo demonstrated that pDCs were antiinflammatory irrespective of their maturation state. These effects were mediated through programmed death-1/programmed death ligand 1 interactions, but not through ICOS ligand, IDO, or IFN-alpha. These findings suggest a specialized immunoregulatory role for pDCs in airway inflammation. Enhancing the antiinflammatory properties of pDCs could be employed as a novel strategy in asthma treatment.
Kool
Mirjam
M
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
van Nimwegen
Menno
M
Willart
Monique A M
MA
Muskens
Femke
F
Boon
Louis
L
Smit
Joost J
JJ
Coyle
Anthony
A
Clausen
Björn E
BE
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
Hammad
Hamida
H
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000276:immunology / Q000378:metabolism; D001249:Asthma / Q000473:pathology*; D018122:B7-1 Antigen / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen; D002633:Chemotaxis; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D012130:Respiratory Hypersensitivity / Q000473:pathology
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; C084881:flt3 ligand protein