RRC ID 51830
著者 Kiniwa T, Enomoto Y, Terazawa N, Omi A, Miyata N, Ishiwata K, Miyajima A.
タイトル NK cells activated by Interleukin-4 in cooperation with Interleukin-15 exhibit distinctive characteristics.
ジャーナル Proc Natl Acad Sci U S A
Abstract Natural killer (NK) cells are known to be activated by Th1-type cytokines, such as IL-2, -12, or -18, and they secrete a large amount of IFN-γ that accelerates Th1-type responses. However, the roles of NK cells in Th2-type responses have remained unclear. Because IL-4 acts as an initiator of Th2-type responses, we examined the characteristics of NK cells in mice overexpressing IL-4. In this study, we report that IL-4 overexpression induces distinctive characteristics of NK cells (B220(high)/CD11b(low)/IL-18Rα(low)), which are different from mature conventional NK (cNK) cells (B220(low)/CD11b(high)/IL-18Rα(high)). IL-4 overexpression induces proliferation of tissue-resident macrophages, which contributes to NK cell proliferation via production of IL-15. These IL-4-induced NK cells (IL4-NK cells) produce higher levels of IFN-γ, IL-10, and GM-CSF, and exhibit high cytotoxicity compared with cNK cells. Furthermore, incubation of cNK cells with IL-15 and IL-4 alters their phenotype to that similar to IL4-NK cells. Finally, parasitic infection, which typically causes strong Th2-type responses, induces the development of NK cells with characteristics similar to IL4-NK cells. These IL4-NK-like cells do not develop in IL-4Rα KO mice by parasitic infection. Collectively, these results suggest a novel role of IL-4 in immune responses through the induction of the unique NK cells.
巻・号 113(36)
ページ 10139-44
公開日 2016-9-6
DOI 10.1073/pnas.1600112113
PII 1600112113
PMID 27551096
PMC PMC5018748
MeSH Animals CD11b Antigen / genetics CD11b Antigen / immunology Cell Proliferation Cytotoxicity, Immunologic* Gene Expression Regulation Granulocyte-Macrophage Colony-Stimulating Factor / genetics Granulocyte-Macrophage Colony-Stimulating Factor / immunology Interferon-gamma / genetics Interferon-gamma / immunology Interleukin-10 / genetics Interleukin-10 / immunology Interleukin-15 / genetics Interleukin-15 / immunology* Interleukin-15 / pharmacology Interleukin-4 / genetics Interleukin-4 / immunology* Interleukin-4 / pharmacology Killer Cells, Natural / drug effects Killer Cells, Natural / immunology* Killer Cells, Natural / parasitology Leukocyte Common Antigens / genetics Leukocyte Common Antigens / immunology Lymphocyte Activation* Macrophages / immunology Macrophages / parasitology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Nippostrongylus / immunology Nippostrongylus / pathogenicity Receptors, Interleukin-18 / genetics Receptors, Interleukin-18 / immunology Receptors, Interleukin-4 / deficiency Receptors, Interleukin-4 / genetics Receptors, Interleukin-4 / immunology Signal Transduction Strongylida Infections / genetics Strongylida Infections / immunology* Strongylida Infections / parasitology
IF 9.412
引用数 12
リソース情報
ヒト・動物細胞 YAC-1(RCB1165)