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

• DOI: 10.1165/rcmb.2006-0020oc
• Publication Date: 2006-12-02T01:33:54Z
• Authors: Stefan Ivanov; Steven Bozinovski; Apostolos Bossios; Hadi Valadi; Ross Vlahos; Carina Malmhäll; Margareta Sjöstrand; Jay K. Kolls; Gary P. Anderson; Anders Lindén
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Mice, Inbred BALB C; Neutrophils; Interleukin-17; Peptidoglycan; Immunohistochemistry; Interleukin-23; Immunity, Innate; 3. Good health; Mice; 03 medical and health sciences; Gelatinases; Animals; Bronchoalveolar Lavage Fluid; Lung

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.