Interleukin-1β Selectively Expands and Sustains Interleukin-22 + Immature Human Natural Killer Cells in Secondary Lymphoid Tissue

• Published in: Immunity (Cambridge, Mass.) Mass.), 2010-06, Vol.32 (6), p.803-814
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: CELLIMMUNO; MOLIMMUNO
• ISSN: 1074-7613; 1097-4180
• 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-1β-producing conventional dendritic cells (cDCs) within SLT. IL-1R1 hi iNK cells required continuous exposure to IL-1β to retain AHR and IL-22 expression, and they proliferate in direct response to cDC-derived IL-15 and IL-1β. In the absence of IL-1β, 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-γ. Thus, cDC-derived IL-1β preserves and expands IL-1R1 hiIL-22 + AHR + iNK cells, potentially influencing human mucosal innate immunity during infection. ► Human stage 3 iNK cells specifically and constitutively coexpress IL-1R1 and IL-22 ► In vitro, IL-1β promotes stage 3 iNK cell expansion and sustains IL-22 and AHR mRNA ► IL-1R1 hi stage 3 iNK cells proliferate in response to IL-15 and IL-1β from SLT cDCs ► IL-1β inhibits stage 3 iNK cell differentiation to IFN-γ, producing mature NK cells