IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice.
BACKGROUND
The IL-23-IL-17A-producing CD4(+) T-cell (Th17 cell) axis plays an important role in the development of chronic inflammatory diseases, including autoimmune diseases. However, the role of the IL-23-Th17 cell axis in the regulation of allergic airway inflammation is still largely unknown.


OBJECTIVE
To determine the role of IL-23 and Th17 cells in allergic airway inflammation.


METHODS
We examined the effect of anti-IL-23 antibody on antigen-induced airway inflammation. We also investigated the effect of enforced expression of IL-23 on allergic airway inflammation by generating lung-specific IL-23 transgenic mice. Moreover, we examined the effect of adoptive transfer of antigen-specific Th17 cells on allergic airway inflammation.


RESULTS
IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation, and the neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. The enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil and neutrophil recruitment into the airways; Th2 cytokine, IL-17A, and tumor necrosis factor (TNF)-alpha production in the airways; goblet cell hyperplasia; and airway hyperresponsiveness. Moreover, IL-23-mediated enhancement of antigen-induced Th2 cytokine production and eosinophil recruitment in the airways was still observed in the mice lacking IL-17A. Furthermore, although adoptive transfer of antigen-specific Th17 cells alone induced neutrophil but not eosinophil recruitment into the airways upon antigen inhalation, cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced Th2-cell-mediated eosinophil recruitment into the airways and airway hyperresponsiveness.


CONCLUSIONS
IL-23 and Th17 cells not only induce Th17-cell-mediated neutrophilic airway inflammation but also up-regulate Th2-cell-mediated eosinophilic airway inflammation.
Wakashin
Hidefumi
H
Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan.
Hirose
Koichi
K
Maezawa
Yuko
Y
Kagami
Shin-ichiro
S
Suto
Akira
A
Watanabe
Norihiko
N
Saito
Yasushi
Y
Hatano
Masahiko
M
Tokuhisa
Takeshi
T
Iwakura
Yoichiro
Y
Puccetti
Paolo
P
Iwamoto
Itsuo
I
Nakajima
Hiroshi
H
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
D020381:Interleukin-17; D053759:Interleukin-23