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Functional relevance of the IL-23-IL-17 axis in lungs in vivo.

Abstract：

: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.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Ivanov S,Bozinovski S,Bossios A,Valadi H,Vlahos R,Malmhäll C,Sjöstrand M,Kolls JK,Anderson GP,Lindén A

doi

10.1165/rcmb.2006-0020OC

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

442-51

issue

4

eissn

1044-1549

issn

1535-4989

pii

2006-0020OC

journal_volume

36

pub_type

杂志文章

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