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

Content Provider	PubMed Central
Author	Kreisel, Daniel Sugimoto, Seiichiro Zhu, Jihong Nava, Ruben Li, Wenjun Okazaki, Mikio Yamamoto, Sumiharu Ibrahim, Mohsen Huang, Howard J. Toth, Kelsey A. Ritter, Jon H. Krupnick, Alexander S. Miller, Mark J. Gelman, Andrew E.
Copyright Year	2011
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.
Related Links	http://dx.doi.org/10.1182/blood-2011-04-347823
Ending Page	6182
Page Count	11
Starting Page	6172
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	23
Volume Number	118
Language	English
Publisher	American Society of Hematology
Publisher Date	2011-12-01
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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