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Functional Relevance of the IL-23–IL-17 Axis in Lungs In Vivo

Lung Pharmacology and Immunology Groups, Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden; Lung Disease Research Group, Cooperative Research Centre for Chronic Inflammatory Diseases, Departments of Pharmacology and Medicine, The University of Melbourne, Parkville, Victoria, Australia; and Division of Pulmonology, Department of Pediatrics, Children's Hospital of Pittsburgh and the University of Pittsburgh, Pittsburgh, Pennsylvania

Correspondence and requests for reprints should be addressed to Stefan Ivanov, M.D., 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. 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 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.

Key Words: interleukin-23 • interleukin-17 • innate response • lungs

CLINICAL RELEVANCE We show that in lungs in vivo, the antigen-presenting cell cytokine IL-23 and the T cell cytokine IL-17 form a functionally relevant "axis" linking innate and adaptive responses in the early phase of host defense.

 

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