• Markus Bosmann, Jamison J Grailer, Norman F Russkamp, Robert Ruemmler, Firas S Zetoune, J Vidya Sarma, and Peter A Ward.
• Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
• Shock. 2013 May 1; 39 (5): 447-52.

AbstractAcute lung injury (ALI) is a severe pulmonary disease causing high numbers of fatalities worldwide. Innate immune responses are an integral part of the pathophysiologic events during ALI. Interleukin 23 (IL-23) is a proinflammatory mediator known to direct the inflammatory responses in various settings of infection, autoimmunity, and cancer. Interleukin 23 has been associated with proliferation and effector functions in T(H)17 cells. Surprisingly, little is known about production of IL-23 during ALI. In this study, we found expression of mRNA for IL-23p19 to be 10-fold elevated in lung homogenates of C57BL/6 mice after lipopolysaccharide (LPS)-induced ALI. Likewise, concentrations of IL-23 significantly increased in bronchoalveolar lavage fluids. Experiments with IL-23-deficient mice showed that endogenous IL-23 was required for production of IL-17A during LPS-ALI. CD11c-diphtheria toxin receptor transgenic mice were used to selectively deplete CD11c cells, the data suggesting that IL-23 production is dependent at least in part on CD11c cells during ALI. No alterations of IL-23 levels were observed in Rag-1-deficient mice as compared with wild-type C57BL/6 mice following ALI. The mouse alveolar macrophage cell line, MH-S, as well as primary alveolar macrophages displayed abundant surface expression of CD11c. Activation of these macrophages by LPS resulted in release of IL-23 in vitro. Our findings identify CD11c macrophages in the lung are likely an important source of IL-23 during ALI, which may be helpful for better understanding of this disease.

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