Hughes Tiffany, Becknell Brian, Freud Aharon G, McClory Susan, Briercheck Edward, Yu Jianhua, Mao Charlene, Giovenzana Chiara, Nuovo Gerard, Wei Lai, Zhang Xiaoli, Gavrilin Mikhail A, Wewers Mark D, Caligiuri Michael A
Integrated Biomedical Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Immunity. 2010 Jun 25;32(6):803-14. doi: 10.1016/j.immuni.2010.06.007.
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-1beta-producing conventional dendritic cells (cDCs) within SLT. IL-1R1(hi) iNK cells required continuous exposure to IL-1beta to retain AHR and IL-22 expression, and they proliferate in direct response to cDC-derived IL-15 and IL-1beta. In the absence of IL-1beta, a substantially greater fraction of IL-1R1(hi) iNK cells differentiated to stage 4 NK cells and acquired the ability to kill and secrete IFN-gamma. Thus, cDC-derived IL-1beta preserves and expands IL-1R1(hi)IL-22(+)AHR(+) iNK cells, potentially influencing human mucosal innate immunity during infection.
在次级淋巴组织（SLT）中的人类自然杀伤（NK）细胞中间体中，3期CD34(-)CD117(+)CD161(+)CD94(-)未成熟NK（iNK）细胞独特地表达芳烃受体（AHR）和白细胞介素-22（IL-22），支持其在黏膜免疫中的作用。控制这些细胞增殖和分化的机制尚不清楚。在此，我们证明白细胞介素-1受体IL-1R1由iNK细胞的一个亚群选择性表达，该亚群定位于SLT内产生IL-1β的传统树突状细胞（cDC）附近。IL-1R1(hi) iNK细胞需要持续暴露于IL-1β以维持AHR和IL-22表达，并且它们直接响应cDC衍生的IL-15和IL-1β而增殖。在没有IL-1β的情况下，相当大比例的IL-1R1(hi) iNK细胞分化为4期NK细胞，并获得杀伤和分泌IFN-γ的能力。因此，cDC衍生的IL-1β保留并扩增IL-1R1(hi)IL-22(+)AHR(+) iNK细胞，可能在感染期间影响人类黏膜固有免疫。
