Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue.
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.
Hughes
Tiffany
T
Integrated Biomedical Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Becknell
Brian
B
Freud
Aharon G
AG
McClory
Susan
S
Briercheck
Edward
E
Yu
Jianhua
J
Mao
Charlene
C
Giovenzana
Chiara
C
Nuovo
Gerard
G
Wei
Lai
L
Zhang
Xiaoli
X
Gavrilin
Mikhail A
MA
Wewers
Mark D
MD
Caligiuri
Michael A
MA
D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097043:Interleukin-22
D053583:Interleukin-1beta; D007378:Interleukins; D017472:Receptors, Interleukin-1; D000097043:Interleukin-22