title: Interleukin-1beta selectively expands and sustains interleukin-22+ immature human natural killer cells in secondary lymphoid tissue.
abstract: 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.
authors.affiliation: Integrated Biomedical Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hughes
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: Aharon G
authors.initials: AG
authors.lastname: Freud
authors.forename: Susan
authors.initials: S
authors.lastname: McClory
authors.forename: Edward
authors.initials: E
authors.lastname: Briercheck
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Charlene
authors.initials: C
authors.lastname: Mao
authors.forename: Chiara
authors.initials: C
authors.lastname: Giovenzana
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Gavrilin
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: 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
chemical_list: D053583:Interleukin-1beta; D007378:Interleukins; D017472:Receptors, Interleukin-1; D000097043:Interleukin-22