Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens.
BACKGROUND
The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice.


METHODS
Allergic airway inflammation was evaluated in wild-type and IL-23p19(-/-) mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immunoglobulins in serum as well as cytokines in bronchoalveolar or peritoneal lavage fluid and lung tissue were determined by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction.


RESULTS
Deficiency of IL-23p19 decreased eosinophils and Th2 cytokines in bronchoalveolar lavage fluid (BALF) of OVA-treated mice, while it increased BALF eosinophils of HDM-treated mice. Peritoneal injection of OVA with alum, but not of HDM, induced local synthesis of IL-6, IL-10, and IL-23. Systemic production of antigen-specific IgG1 was partially dependent on IL-23. In contrast, airway exposure to HDM, but not to OVA, induced IL-23p19 mRNA expression in the lungs. In IL-23p19-deficient mice, HDM-exposed lungs did not exhibit the induction of IL-17A, which negatively regulates eosinophilic inflammation.


CONCLUSIONS
Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation.
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Rika
R
Ogawa
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; MSD Endowed Program for Allergy Research, Keio University School of Medicine, Tokyo, Japan. Electronic address: yu_ske_suzuki@yahoo.co.jp.
Yusuke
Y
Suzuki
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; MSD Endowed Program for Allergy Research, Keio University School of Medicine, Tokyo, Japan.
Shizuko
S
Kagawa
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Katsunori
K
Masaki
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Koichi
K
Fukunaga
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
Akihiko
A
Yoshimura
Center for General Medicine and Education, Keio University School of Medicine, Tokyo, Japan.
Seitaro
S
Fujishima
Division of Pulmonary Medicine, Department of Internal Medicine, Tokyo Dental College, Chiba, Japan.
Takeshi
T
Terashima
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Tomoko
T
Betsuyaku
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan; Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Koichiro
K
Asano
D000485:Allergens; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010529:Peritoneal Cavity; D039981:Pyroglyphidae / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D000941:Antigens; D016207:Cytokines; D053759:Interleukin-23; D010047:Ovalbumin
Asthma; Eosinophils; Interleukin-17A; Interleukin-23; Th17