In vivo role of Flt3 ligand and dendritic cells in NK cell homeostasis

Martin Guimond, Aharon G. Freud, Hsiaoyin C. Mao, Jianhua Yu, Bradley W. Blaser, Jeffrey W. Leong, Jeffrey B. Vandeusen, Adrienne Dorrance, Jianying Zhang, Crystal L. Mackall, Michael A. Caligiuri

Research output: Contribution to journalArticle

Abstract

IL-15 is required for NK cell development and homeostasis in vivo. Because IL-15 is presented in trans via its high-affinity IL-15Rα-chain to cells expressing the IL-15Rβγ complex, we postulated that certain IL-15-bearing cells must be required for NK cell homeostasis. Using IL-15 WT/WT and IL-15-/- mice, bone marrow chimeras with normal cellularity, and a selective depletion of CD11chi dendritic cells (DCs), we demonstrate that ablation of the resting CD11chi DC population results in a highly significant decrease in the absolute number of mature NK cells. In contrast, administration of Flt3 ligand increases the CD11chi DC population, which, when expressing IL-15, significantly expands mature NK cells via enhanced survival and proliferation. In summary, a CD11chi DC population expressing IL-15 is required to maintain NK cell homeostasis under conditions of normal cellularity and also is required to mediate Flt3 ligand-induced NK cell expansion in vivo.

Original languageEnglish (US)
Pages (from-to)2769-2775
Number of pages7
JournalJournal of Immunology
Volume184
Issue number6
DOIs
StatePublished - Mar 15 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Guimond, M., Freud, A. G., Mao, H. C., Yu, J., Blaser, B. W., Leong, J. W., Vandeusen, J. B., Dorrance, A., Zhang, J., Mackall, C. L., & Caligiuri, M. A. (2010). In vivo role of Flt3 ligand and dendritic cells in NK cell homeostasis. Journal of Immunology, 184(6), 2769-2775. https://doi.org/10.4049/jimmunol.0900685