IL-17A Is Critical for CD8+ T Effector Response in Airway Epithelial Injury After Transplantation

Transplantation
Ruochan ZhangJiang-Nan Xu

Abstract

Airway epithelium is the primary target of trachea and lung transplant rejection, the degree of epithelial injury is closely correlated with obliterative bronchiolitis development. In this study, we investigated the cellular and molecular mechanisms of IL-17A-mediated airway epithelial injury after transplantation. Murine orthotopic allogeneic trachea or lung transplants were implemented in wild type or RORγt mice. Recipients received anti-IL-17A or anti-IFNγ for cytokine neutralization, anti-CD8 for CD8 T-cell depletion, or STAT3 inhibitor to suppress type 17 CD4+/CD8+ T cell development. Airway injury and graft inflammatory cell infiltration were examined by histopathology and immunohistochemistry. Gene expression of IL-17A, IFNγ, perforin, granzyme B, and chemokines in grafts was quantitated by real-time RT-PCR. IL-17A and IFNγ were rapidly expressed and associated with epithelial injury and CD8 T-cell accumulation after allotransplantation. Depletion of CD8 T cells prevented airway epithelial injury. Neutralization of IL-17A or devoid of IL-17A production by RORγt deficiency improved airway epithelial integrity of the trachea allografts. Anti-IL-17A reduced the expression of CXCL9, CXCL10, CXCL11, and CCL20, and abolished C...Continue Reading

References

Sep 9, 1998·American Journal of Respiratory Cell and Molecular Biology·I P NeuringerR M Aris
Dec 1, 2001·Transplantation·C A RumbleyS M Phillips
Jul 5, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·John A BelperioRobert M Strieter
Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·John A BelperioRobert M Strieter
Dec 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·David M RichardsDaniel L Mueller
Feb 14, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Félix G FernándezT Mohanakumar
Jan 26, 2005·Pediatric Transplantation·Andrés JaramilloT Mohanakumar
Mar 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomohiro MurakawaMark R Nicolls
Oct 1, 2005·American Journal of Respiratory Cell and Molecular Biology·Erin E WestJohn F McDyer
Jun 27, 2006·The Journal of Biological Chemistry·Fang ShenSarah L Gaffen
Sep 26, 2006·The Annals of Thoracic Surgery·Elbert KuoT Mohanakumar
Feb 6, 2007·The Journal of Biological Chemistry·Xuexian O YangChen Dong
Jul 7, 2007·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Gregory I SnellTom C Kotsimbos
Dec 22, 2007·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Susan StewartSamuel A Yousem
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew E GelmanDaniel Kreisel
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bryna E BurrellD Keith Bishop
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bogoljub CiricAbdolmohamad Rostami
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danielle D KishRobert L Fairchild
May 28, 2009·Blood·Christian S HinrichsNicholas P Restifo
Jun 23, 2009·European Journal of Immunology·Magdalena HuberMichael Lohoff
Oct 3, 2009·Science·Ashutosh ChaudhryAlexander Y Rudensky
Dec 10, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vedran RadojcicLeo Luznik
Mar 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria de la Luz Garcia-HernandezRichard W Dutton
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kristin J Ness-SchwickerathCraig T Morita
Oct 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sheng XuXuetao Cao
Apr 28, 2011·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·L FanD S Wilkes
Jul 26, 2011·Nature Reviews. Immunology·Alberto MantovaniSébastien Jaillon
Oct 4, 2011·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Jason D ChristieMarshall I Hertz
Dec 22, 2011·Current Opinion in Organ Transplantation·Farida AbadjaMohammed J Ansari
Jan 15, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yu YuXue-Zhong Yu
Jan 22, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·P H LemaîtreA Le Moine
Jan 26, 2013·Nature Reviews. Immunology·Hergen SpitsEric Vivier
Feb 19, 2013·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Stijn E VerledenBart M Vanaudenaerde
Feb 8, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·C A SuR L Fairchild
Oct 7, 2014·American Journal of Respiratory Cell and Molecular Biology·Elizabeth A LendermonJohn F McDyer
Dec 2, 2014·Current Transplantation Reports·Charles A Su, Robert L Fairchild
Mar 17, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Q WuR A Shilling

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Citations

Oct 3, 2019·Current Opinion in Organ Transplantation·Anna B Morris, Mandy L Ford
Aug 7, 2019·Scientific Reports·Constanca FigueiredoBettina Wiegmann
Oct 16, 2020·Expert Review of Respiratory Medicine·Ashwini ArjunaThalachallour Mohanakumar
Sep 23, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Markus QuanteStefan G Tullius

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