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Central Role of Conventional Dendritic Cells in Regulation of Bone Marrow Release and Survival of Neutrophils

Jingjing Jiao, Ana-Cristina Dragomir, Peri Kocabayoglu, Adeeb H. Rahman, Andrew Chow, Daigo Hashimoto, Marylene Leboeuf, Thomas Kraus, Thomas Moran, Gonzalo Carrasco-Avino, Scott L. Friedman, Miriam Merad and Costica Aloman
J Immunol March 3, 2014, 1300237; DOI: https://doi.org/10.4049/jimmunol.1300237
Jingjing Jiao
*Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Ana-Cristina Dragomir
*Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Peri Kocabayoglu
*Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Adeeb H. Rahman
*Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Andrew Chow
†Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Daigo Hashimoto
†Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Marylene Leboeuf
†Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Thomas Kraus
‡Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Thomas Moran
‡Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Gonzalo Carrasco-Avino
§Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Scott L. Friedman
*Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Miriam Merad
†Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
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Costica Aloman
*Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
¶Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois, Chicago, IL 60612; and
‖Division of Transplant Surgery, Department of Surgery, University of Illinois, Chicago, IL 60612
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Abstract

Neutrophils are the most abundant cell type in the immune system and play an important role in the innate immune response. Using a diverse range of mouse models with either defective dendritic cell (DC) development or conditional DC depletion, we provide in vivo evidence indicating that conventional DCs play an important role in the regulation of neutrophil homeostasis. Flk2, Flt3L, and Batf3 knockout mice, which have defects in DC development, have increased numbers of liver neutrophils in the steady state. Conversely, neutrophil frequency is reduced in DC-specific PTEN knockout mice, which have an expansion of CD8+ and CD103+ DCs. In chimeric CD11c-DTR mice, conventional DC depletion results in a systemic increase of neutrophils in peripheral organs in the absence of histological inflammation or an increase in proinflammatory cytokines. This effect is also present in splenectomized chimeric CD11c-DTR mice and is absent in chimeric mice with 50% normal bone marrow. In chimeric CD11c-DTR mice, diphtheria toxin treatment results in enhanced neutrophil trafficking from the bone marrow into circulation and increased neutrophil recruitment. Moreover, there is an increased expression of chemokines/cytokines involved in neutrophil homeostasis and reduced neutrophil apoptosis. These data underscore the role of the DC pool in regulating the neutrophil compartment in nonlymphoid organs.

Footnotes

  • This work was supported by National Institutes of Health Grant 1K08DK088954 (to C.A.). A.-C.D. was supported by the Levine Family Foundation. S.L.F. is supported by National Institutes of Health Grants DK56621 and AA020709. M.M. is supported by National Institutes of Health Grants R01 CA154947A, AI10008, and AI 089987.

  • The online version of this article contains supplemental material.

  • Received January 24, 2013.
  • Accepted January 28, 2014.
  • Copyright © 2014 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 206 (3)
The Journal of Immunology
Vol. 206, Issue 3
1 Feb 2021
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Central Role of Conventional Dendritic Cells in Regulation of Bone Marrow Release and Survival of Neutrophils
Jingjing Jiao, Ana-Cristina Dragomir, Peri Kocabayoglu, Adeeb H. Rahman, Andrew Chow, Daigo Hashimoto, Marylene Leboeuf, Thomas Kraus, Thomas Moran, Gonzalo Carrasco-Avino, Scott L. Friedman, Miriam Merad, Costica Aloman
The Journal of Immunology March 3, 2014, 1300237; DOI: 10.4049/jimmunol.1300237

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Central Role of Conventional Dendritic Cells in Regulation of Bone Marrow Release and Survival of Neutrophils
Jingjing Jiao, Ana-Cristina Dragomir, Peri Kocabayoglu, Adeeb H. Rahman, Andrew Chow, Daigo Hashimoto, Marylene Leboeuf, Thomas Kraus, Thomas Moran, Gonzalo Carrasco-Avino, Scott L. Friedman, Miriam Merad, Costica Aloman
The Journal of Immunology March 3, 2014, 1300237; DOI: 10.4049/jimmunol.1300237
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Print ISSN 0022-1767        Online ISSN 1550-6606