Functional relevance of the IL-23-IL-17 axis in lungs in vivo.
It is known that interleukin (IL)-23, an IL-12-family cytokine, can be released by certain antigen-presenting cells in response to bacterial pathogens. Recent in vitro studies indicate that this cytokine stimulates a unique subset of CD4 cells, the T helper cell (Th)17 subset, to produce and release the proinflammatory cytokine IL-17. However, it has not been known whether this is an action of IL-23 per se that has bearing for the early innate response in lungs in vivo and whether there is an IL-23-responsive population of IL-17-producing CD4 cells in the bronchoalveolar space. We now present evidence that IL-23 can be involved in the early innate response to both gram-negative and gram-positive bacterial products in the lungs: Recombinant IL-23 protein per se accumulates inflammatory cells in the bronchoalveolar space in part via endogenous production of IL-17, and this IL-17 production occurs locally in IL-23-responsive CD4 cells. This IL-17 response to IL-23 occurs without any pronounced impact on Th1/Th2 polarization. Moreover, recombinant IL-23 protein increases the local MMP-9 activity, which is generated by neutrophils mainly. CD4 cells in the lungs may thus respond to IL-23 from antigen-presenting cells exposed to gram-negative and gram-positive pathogens and thereby reinforce the early innate response. These findings support that IL-23 and IL-17 form a functionally relevant "immunological axis" in the lungs in vivo.
Ivanov
Stefan
S
Lung Pharmacology & Immunology Groups, Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy at Göteborg University, Guldhedsgatan 10A, S-413 46 Gothenburg, Sweden. Stefan.Ivanov@lungall.gu.se
Bozinovski
Steven
S
Bossios
Apostolos
A
Valadi
Hadi
H
Vlahos
Ross
R
Malmhäll
Carina
C
Sjöstrand
Margareta
M
Kolls
Jay K
JK
Anderson
Gary P
GP
Lindén
Anders
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018093:Gelatinases; D007113:Immunity, Innate; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000502:physiology; D010457:Peptidoglycan / Q000494:pharmacology
D020381:Interleukin-17; D053759:Interleukin-23; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D018093:Gelatinases