Exacerbated Th2-mediated airway inflammation and hyperresponsiveness in autoimmune diabetes-prone NOD mice: a critical role for CD1d-dependent NKT cells.
The NOD mouse has proved to be a relevant model of insulin-dependent diabetes mellitus, closely resembling the human disease. However, it is unknown whether this strain presents a general biastoward Th1-mediated autoimmunity or remains capable of mounting complete Th2-mediated responses. Here, we show that NOD mice have the capacity to develop a typical Th2-mediated disease, namely experimental allergic asthma. In contrast to what might have been expected, they even developed a stronger Th2-mediated pulmonary inflammatory response than BALB/c mice, a strain that shows a typical Th2 bias in this model. Thus, after allergen sensitization and intra-nasal challenge, the typical features of experimental asthma were exacerbated in NOD mice, including enhanced bronchopulmonary responsiveness, mucus production and eosinophilic inflammation in the lungs as well as specific IgE titers in serum. These hallmarks of allergic asthma were associated with increased IL-4, IL-5, IL-13 and eotaxin production in the lungs, as compared with BALB/c mice. Notwithstanding their quantitative and functional defect in NOD mice, CD1d-dependent NKT cells contribute to aggravate the disease, since in OVA-immunized CD1d(-/-) NOD mice, which are deficient in this particular T cell subset, airway eosinophilia was clearly diminished relative to NOD littermates. This is the first evidence that autoimmune diabetes-prone NOD mice can also give rise to enhanced Th2-mediated responses and might thus provide a useful model for the study of common genetic and cellular components, including NKT cells that contribute to both asthma and type 1 diabetes.
Araujo
Luiza M
LM
CNRS FRE 2444, Paris V, Hôpital Necker, Paris, France.
Lefort
Jean
J
Nahori
Marie-Anne
MA
Diem
Séverine
S
Zhu
Ren
R
Dy
Michel
M
Leite-de-Moraes
Maria C
MC
Bach
J F
JF
Vargaftig
B Boris
BB
Herbelin
André
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D009093:Mucus / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; C515456:CCL11 protein, human; C526877:CD1D protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5; D007073:Immunoglobulin E; D010047:Ovalbumin