Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue.

Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue.
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DOI:
10.1016/j.immuni.2010.06.007
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发表时间:
2010-06-25
期刊:
影响因子:
32.4
通讯作者:
Caligiuri MA
Caligiuri MA
中科院分区:
医学1区
文献类型:
--
作者:
Hughes T;Becknell B;Freud AG;McClory S;Briercheck E;Yu J;Mao C;Giovenzana C;Nuovo G;Wei L;Zhang X;Gavrilin MA;Wewers MD;Caligiuri MA

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Among human natural killer (NK) cell intermediates in secondary lymphoid tissue (SLT), stage 3 CD34− CD117+CD161+CD94− immature NK (iNK) cells uniquely express aryl hydrocarbon receptor (AHR) and interleukin-22 (IL-22), supporting a role in mucosal immunity. The mechanisms controlling proliferation and differentiation of these cells are unknown. Here we demonstrate that the IL-1 receptor IL-1R1 was selectively expressed by a subpopulation of iNK cells that localized proximal to IL-1β-producing conventional dendritic cells (cDCs) within SLT. IL-1R1hi iNK cells required continuous exposure to IL-1β to retain AHR and IL-22 expression, and proliferate in direct response to cDC-derived IL-15 and IL-1β. In the absence of IL-1β, a substantially greater fraction of IL-1R1hi iNK cells differentiated to stage 4 NK cells and acquired the ability to kill and secrete IFN-γ. Thus, cDC-derived IL-1β preserves and expands IL-1R1hiIL-22+AHR+ iNK cells, potentially influencing human mucosal innate immunity during infection.
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