Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance

Daniel Kreisel, Seiichiro Sugimoto, Jihong Zhu, Ruben Nava, Wenjun Li, Mikio Okazaki, Sumiharu Yamamoto, Mohsen Ibrahim, Howard J. Huang, Kelsey A. Toth, Jon H. Ritter, Alexander S. Krupnick, Mark J. Miller, Andrew E. Gelman

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62 Citations (Scopus)

Abstract

The mechanisms by which innate immune signals regulate alloimmune responses remain poorly understood. In the present study, we show by intravital 2-photon microscopy direct interactions between graft-infiltrating neutrophils and donor CD11c + dendritic cells (DCs) within orthotopic lung allografts immediately after reperfusion. Neutrophils isolated from the airways of lung transplantation recipients stimulate donor DCs in a contact-dependent fashion to augment their production of IL-12 and expand alloantigen-specific IFN-γ + T cells. DC IL-12 expression is largely regulated by degranulation and induced by TNF-α associated with the neutrophil plasma membrane. Extended cold ischemic graft storage enhances G-CSF-mediated granulopoiesis and neutrophil graft infiltration, resulting in exacerbation of ischemia-reperfusion injury after lung transplantation. Ischemia reperfusion injury prevents immunosuppression- mediated acceptance of mouse lung allografts unless G-CSF-mediated granulopoiesis is inhibited. Our findings identify granulopoiesis-mediated augmentation of alloimmunity as a novel link between innate and adaptive immune responses after organ transplantation.

Original languageEnglish
Pages (from-to)6172-6182
Number of pages11
JournalBlood
Volume118
Issue number23
DOIs
Publication statusPublished - Dec 1 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Kreisel, D., Sugimoto, S., Zhu, J., Nava, R., Li, W., Okazaki, M., Yamamoto, S., Ibrahim, M., Huang, H. J., Toth, K. A., Ritter, J. H., Krupnick, A. S., Miller, M. J., & Gelman, A. E. (2011). Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance. Blood, 118(23), 6172-6182. https://doi.org/10.1182/blood-2011-04-347823