A novel pathway that regulates inflammatory disease in the respiratory tract.
In animals with acute airway inflammation followed by repeated exposure to inhaled Ag, inflammation wanes over time and thus limits the study of chronic airway inflammatory diseases such as asthma. We developed a model of airway inflammation and inhalational exposure to investigate regulatory pathways in the respiratory tract. We show that Th1- and Th2-induced airway inflammation followed by repeated exposure to inhaled Ag leads to a state of immunosuppression. Challenge of these animals with a marked population of TCR transgenic effector Th1 or Th2 cells results in a striking inhibition of inflammation and effector Th cells. In Th2 models, airway hyperresponsiveness, mucus, and eosinophilia are reduced. The inhibitory effects observed are Ag nonspecific, can be induced in lymphocyte-deficient mice, and are associated with a population of TGF-beta1-expressing macrophages. Induction of this pathway may offer potent localized treatment of chronic T cell-mediated respiratory illnesses and provide insights into the development of such diseases.
Niu
Naiqian
N
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Le Goff
Marc K
MK
Li
Fangyong
F
Rahman
Marina
M
Homer
Robert J
RJ
Cohn
Lauren
L
D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002908:Chronic Disease; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000276:immunology
D000941:Antigens; D053773:Transforming Growth Factor beta1