TGF-beta regulates airway responses via T cells.
Allergic asthma is characterized by airway hyperreactivity, inflammation, and a Th2-type cytokine profile favoring IgE production. Beneficial effects of TGF-beta and conflicting results regarding the role of Th1 cytokines have been reported from murine asthma models. In this study, we examined the T cell as a target cell of TGF-beta-mediated immune regulation in a mouse model of asthma. We demonstrate that impairment of TGF-beta signaling in T cells of transgenic mice expressing a dominant-negative TGF-beta type II receptor leads to a decrease in airway reactivity in a non-Ag-dependent model. Increased serum levels of IFN-gamma can be detected in these animals. In contrast, after injection of OVA adsorbed to alum and challenge with OVA aerosol, transgenic animals show an increased airway reactivity and inflammation compared with those of wild-type animals. IL-13 levels in bronchoalveolar lavage fluid and serum as well as the number of inducible NO synthase-expressing cells in lung infiltrates were increased in transgenic animals. These results demonstrate an important role for TGF-beta signaling in T cells in the regulation of airway responses and suggest that the beneficial effects observed for TGF-beta in airway hyperreactivity and inflammation may be due to its regulatory effects on T cells.
Schramm
Christoph
C
I. Medizinische Klinik, Johannes Gutenberg University, Mainz, Germany. schramm@mail.uni-mainz.de
Herz
Udo
U
Podlech
Jürgen
J
Protschka
Martina
M
Finotto
Susetta
S
Reddehase
Matthias J
MJ
Köhler
Heinz
H
Galle
Peter R
PR
Lohse
Ansgar W
AW
Blessing
Manfred
M
D000280:Administration, Inhalation; D000336:Aerosols; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000918:Antibody Specificity; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018801:CD2 Antigens / Q000235:genetics; D002465:Cell Movement; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D018793:Interleukin-13 / Q000096:biosynthesis / Q000097:blood; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology*
D000336:Aerosols; D000534:Alum Compounds; D018801:CD2 Antigens; D018984:Epitopes, T-Lymphocyte; D018793:Interleukin-13; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C041524:aluminum sulfate; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II