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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900995v1 183/8/5301    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Crowe, C. R. Articles by Kolls, J. K. PubMed PubMed Citation Articles by Crowe, C. R. Articles by Kolls, J. K.

Critical Role of IL-17RA in Immunopathology of Influenza Infection

Christopher R. Crowe,^* Kong Chen, Derek A. Pociask,^* John F. Alcorn,^* Cameron Krivich,^* Richard I. Enelow, Ted M. Ross, Joseph L. Witztum,^¶ and Jay K. Kolls^1*

^*Children’s Hospital of Pittsburgh, Pittsburgh, PA 15213; Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112; Department of Medicine and Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261; and ^¶Department of Medicine, University of California, San Diego, La Jolla, CA 92093

Acute lung injury due to influenza infection is associated with high mortality, an increase in neutrophils in the airspace, and increases in tissue myeloperoxidase (MPO). Because IL-17A and IL-17F, ligands for IL-17 receptor antagonist (IL-17RA), have been shown to mediate neutrophil migration into the lung in response to LPS or Gram-negative bacterial pneumonia, we hypothesized that IL-17RA signaling was critical for acute lung injury in response to pulmonary influenza infection. IL-17RA was critical for weight loss and both neutrophil migration and increases in tissue myeloperoxidase (MPO) after influenza infection. However, IL-17RA was dispensable for the recruitment of CD8⁺ T cells specific for influenza hemagglutinin or nucleocapsid protein. Consistent with this, IL-17RA was not required for viral clearance. However, in the setting of influenza infection, IL-17RA^–/– mice showed significantly reduced levels of oxidized phospholipids, which have previously been shown to be an important mediator in several models of acute lung injury, including influenza infection and gastric acid aspiration. Taken together, these data support targeting IL-17 or IL-17RA in acute lung injury due to acute viral infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Jay K. Kolls, Department of Genetics, Louisiana State University Health Sciences Center, Clinical Sciences Research Building 657, 533 Bolívar Street, New Orleans, LA 70112. E-mail address: jkolls{at}lsuhsc.edu

² Abbreviations used in this paper: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; TRIF, Toll/IL-1R domain-containing adapter-inducing IFN-β; ROI, reactive oxygen intermediate; BAL, bronchoalveolar lavage; BALF, BAL fluid; LDH, lactate dehydrogenase; NP, nucleocapsid protein; HA, hemagglutinin; dpi, days postinfection; KC, CXCL1; MPO, myeloperoxidase.

³ The online version of this article contains supplemental material.

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The JI 2009 183: 4829-4830. [Full Text]