Monocytes control natural killer cell differentiation to effector phenotypes
Autor: | Thierry Walzer, Nico van Rooijen, Frederic Geissmann, Nick Powell, Carmelo Luci, Andrés Hidalgo, Graham M. Lord, Katrina Soderquest, Alfonso Martín-Fontecha |
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Přispěvatelé: | Molecular cell biology and Immunology, CCA - Immuno-pathogenesis |
Rok vydání: | 2011 |
Předmět: |
Adoptive cell transfer
Cellular differentiation Immunology Mice Transgenic Cell Communication Biology Biochemistry Monocytes Natural killer cell Natural killer cell differentiation Immunophenotyping 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine NK-92 Neoplasms medicine Animals Humans Cells Cultured 030304 developmental biology 0303 health sciences Mice Inbred BALB C Lymphokine-activated killer cell CD11b Antigen Histocompatibility Antigens Class I Cell Differentiation Cell Biology Hematology 3. Good health Cell biology Tumor Necrosis Factor Receptor Superfamily Member 7 Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Phenotype Interleukin 12 T-Box Domain Proteins Neoplasm Transplantation Spleen 030215 immunology |
Zdroj: | Blood, 117(17), 4511-4518. American Society of Hematology Europe PubMed Central Soderquest, K, Powell, N, Luci, C, van Rooijen, N, Hidalgo, A, Geissmann, F, Walzer, T, Lord, G M & Martin-Fontecha, A 2011, ' Monocytes control natural killer cell differentiation to effector phenotypes ', Blood, vol. 117, no. 17, pp. 4511-4518 . https://doi.org/10.1182/blood-2010-10-312264 |
ISSN: | 0006-4971 |
DOI: | 10.1182/blood-2010-10-312264 |
Popis: | Natural killer (NK) cells play a major role in immunologic surveillance of cancer. Whether NK-cell subsets have specific roles during antitumor responses and what the signals are that drive their terminal maturation remain unclear. Using an in vivo model of tumor immunity, we show here that CD11bhiCD27low NK cells migrate to the tumor site to reject major histocompatibility complex class I negative tumors, a response that is severely impaired in Txb21−/− mice. The phenotypical analysis of Txb21-deficient mice shows that, in the absence of Txb21, NK-cell differentiation is arrested specifically at the CD11bhiCD27hi stage, resulting in the complete absence of terminally differentiated CD11bhiCD27low NK cells. Adoptive transfer experiments and radiation bone marrow chimera reveal that a Txb21+/+ environment rescues the CD11bhiCD27hi to CD11bhiCD27low transition of Txb21−/− NK cells. Furthermore, in vivo depletion of myeloid cells and in vitro coculture experiments demonstrate that spleen monocytes mediate the terminal differentiation of peripheral NK cells in a Txb21- and IL-15Rα–dependent manner. Together, these data reveal a novel, unrecognized role for Txb21 expression in monocytes in promoting NK-cell development and help appreciate how various NK-cell subsets are generated and participate in antitumor immunity. |
Databáze: | OpenAIRE |
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