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Skuljec J, Chmielewski M, Happle C, et al. Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma. Front Immunol. 2017;8:1125doi: 10.3389/fimmu.2017.01125.
Skuljec, J., Chmielewski, M., Happle, C., Habener, A., Busse, M., Abken, H., & Hansen, G. (2017). Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma. Frontiers in immunology, 81125. https://doi.org/10.3389/fimmu.2017.01125
Skuljec, Jelena, et al. "Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma." Frontiers in immunology vol. 8 (2017): 1125. doi: https://doi.org/10.3389/fimmu.2017.01125
Skuljec J, Chmielewski M, Happle C, Habener A, Busse M, Abken H, Hansen G. Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma. Front Immunol. 2017 Sep 12;8:1125. doi: 10.3389/fimmu.2017.01125. eCollection 2017. PMID: 28955341; PMCID: PMC5600908.
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Front Immunol. 2017 Sep 12;8:1125. doi: 10.3389/fimmu.2017.01125. eCollection 2017.

Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma.

Frontiers in immunology

Jelena Skuljec, Markus Chmielewski, Christine Happle, Anika Habener, Mandy Busse, Hinrich Abken, Gesine Hansen

Affiliations

  1. Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
  2. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
  3. Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
  4. Clinic I Internal Medicine, University Hospital Cologne, Cologne, Germany.

PMID: 28955341 PMCID: PMC5600908 DOI: 10.3389/fimmu.2017.01125

Abstract

Cellular therapy with chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg)-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR) and a chronic, T helper-2 (Th2) cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.

Keywords: adoptive cell therapy; allergic asthma; chimeric antigen receptor; ovalbumin mouse model; regulatory T cells

References

  1. Immunity. 2007 Oct;27(4):635-46 - PubMed
  2. Chest. 2010 Oct;138(4):905-12 - PubMed
  3. J Clin Invest. 2010 Mar;120(3):883-93 - PubMed
  4. Clin Immunol. 2014 Jan;150(1):51-63 - PubMed
  5. J Neuroinflammation. 2012 May 30;9:112 - PubMed
  6. J Exp Med. 2005 Dec 5;202(11):1539-47 - PubMed
  7. J Allergy Clin Immunol. 2009 Apr;123(4):735-46; quiz 747-8 - PubMed
  8. Gastroenterology. 2012 Oct;143(4):1095-107.e2 - PubMed
  9. Nat Med. 2012 May 04;18(5):716-25 - PubMed
  10. J Exp Med. 2007 Jun 11;204(6):1303-10 - PubMed
  11. J Allergy Clin Immunol. 2007 May;119(5):1258-66 - PubMed
  12. Eur Respir J. 2014 Feb;43(2):343-73 - PubMed
  13. Nat Immunol. 2010 Jul;11(7):577-84 - PubMed
  14. J Exp Med. 2006 Nov 27;203(12):2649-60 - PubMed
  15. Front Immunol. 2013 Nov 11;4:371 - PubMed
  16. Nat Immunol. 2008 Mar;9(3):239-44 - PubMed
  17. Am J Respir Cell Mol Biol. 1995 May;12(5):477-87 - PubMed
  18. J Allergy Clin Immunol. 2008 Sep;122(3):617-24.e6 - PubMed
  19. Mol Ther. 2014 May;22(5):1018-28 - PubMed
  20. J Immunol. 2011 Jun 1;186(11):6329-37 - PubMed
  21. PLoS One. 2012;7(7):e40314 - PubMed
  22. Gastroenterology. 2008 Jun;134(7):2014-24 - PubMed
  23. J Allergy Clin Immunol. 2009 Apr;123(4):933-9.e10 - PubMed
  24. J Immunol. 2008 Dec 15;181(12):8209-13 - PubMed
  25. J Exp Med. 2008 Nov 24;205(12):2887-98 - PubMed
  26. Lancet. 2004 Feb 21;363(9409):608-15 - PubMed
  27. Clin Dev Immunol. 2012;2012:721817 - PubMed
  28. Haematologica. 2011 Sep;96(9):1357-65 - PubMed
  29. Blood. 2014 Apr 24;123(17):2625-35 - PubMed
  30. Trends Immunol. 2011 Sep;32(9):420-7 - PubMed
  31. J Exp Med. 2004 Jun 7;199(11):1455-65 - PubMed
  32. Eur Respir Rev. 2013 Sep 1;22(129):251-7 - PubMed
  33. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16717-22 - PubMed
  34. J Immunol. 2008 Nov 15;181(10):6889-97 - PubMed
  35. J Immunol. 2010 Sep 1;185(5):2675-9 - PubMed
  36. Nature. 2012 Feb 08;482(7385):395-9 - PubMed
  37. J Allergy Clin Immunol. 2008 Nov;122(5):1022-1030.e5 - PubMed
  38. Eur J Immunol. 2009 Apr;39(4):1108-17 - PubMed
  39. Int Immunol. 2009 Oct;21(10):1105-11 - PubMed
  40. J Allergy Clin Immunol. 2014 Nov;134(5):1175-1186.e7 - PubMed
  41. Chest. 2015 Oct;148(4):843-844 - PubMed
  42. J Exp Med. 2007 Jun 11;204(6):1257-65 - PubMed
  43. J Immunol. 2007 Jun 1;178(11):6725-9 - PubMed
  44. Gene Ther. 2009 Sep;16(9):1088-96 - PubMed
  45. Clin Exp Allergy. 2012 May;42(5):650-8 - PubMed

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