Published ahead of print on December 1, 2006, doi:10.1165/rcmb.2006-0020OC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 4, April 2007, 442-451 A more recent version of this article appeared on April 1, 2007
Submitted on January 18, 2006 Functional Relevance of the IL-23-IL-17 Axis in Lungs in vivoStefan Ivanov1*,1 Department of Internal Medicine/Respiratory Medicine and Allergology, Lung Pharmacology and Immunology Groups, Sahlgrenska Academy at Goteborg University, Institute of Medicine, Gothenburg, Sweden, 2 Departments of Pharmacology and Medicine, Lung Disease Research Group, Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia, 3 Department of Pediatrics, Division of Pulmonology, Children's Hospital of Pittsburgh and the University of Pittsburgh, Pittsburgh, Philadelphia, USA * To whom correspondence should be addressed. E-mail: Stefan.Ivanov{at}lungall.gu.se.
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 TH-17 subset, to produce and release the pro-inflammatory 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.
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