Induction of tolerance to innocuous inhaled antigen relies on a CCR7-dependent dendritic cell-mediated antigen transport to the bronchial lymph node.
Allergic airway diseases such as asthma are caused by a failure of the immune system to induce tolerance against environmental Ags. The underlying molecular and cellular mechanisms that initiate tolerance are only partly understood. In this study, we demonstrated that a CCR7-dependent migration of both CD103+ and CD103- lung dendritic cells (DC) to the bronchial lymph node (brLN) is indispensable for this process. Although inhaled Ag is amply present in the brLN of CCR7-deficient mice, T cells cannot be tolerized because of the impaired migration of Ag-carrying DC and subsequent transport of Ag from the lung to the draining lymph node. Consequently, the repeated inhalation of Ag protects wild-type but not CCR7-deficient mice from developing allergic airway diseases. Thus, the continuous DC-mediated transport of inhaled Ag to the brLN is critical for the induction of tolerance to innocuous Ags.
Hintzen
Gabriele
G
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Ohl
Lars
L
del Rio
Maria-Luisa
ML
Rodriguez-Barbosa
Jose-Ignacio
JI
Pabst
Oliver
O
Kocks
Jessica R
JR
Krege
Janet
J
Hardtke
Svenja
S
Förster
Reinhold
R
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000235:genetics; D039001:Integrin alpha Chains / Q000096:biosynthesis; D007442:Intubation, Intratracheal; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000941:Antigens; D015703:Antigens, CD; C515371:Ccr7 protein, mouse; D039001:Integrin alpha Chains; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C091367:alpha E integrins; D010047:Ovalbumin