title: Kruppel-like factor 4 (KLF4) promotes the survival of natural killer cells and maintains the number of conventional dendritic cells in the spleen.
abstract: The development and survival of NK cells rely on a complex, spatiotemporal gene expression pattern regulated by specific transcription factors in NK cells and tissue-specific microenvironments supported by hematopoietic cells. Here, we show that somatic deletion of the KLF4 gene, using inducible and lineage-specific cre-transgenic mice, leads to a significant reduction of NK cells (NK1.1(+) TCR-β(-)) in the blood and spleen but not in the BM, liver, or LNs. Functional and immunophenotypic analyses revealed increased apoptosis of CD27(+/-) CD11b(+) NK cells in the spleen of KLF4-deficient mice, although remaining NK cells were able to lyse tumor target cells and produce IFN-γ. A normal recovery of adoptively transferred KLF4-deficient NK cells in WT hosts suggested that the survival defect was not intrinsic of NK cells. However, BM chimeras using KLF4-deficient mice as donors indicated that reduced survival of NK cells depended on BM-derived hematopoietic cells in the spleen. The number of CD11c(hi) DCs, which are known to support NK cell survival, was reduced significantly in the spleen of KLF4-deficient mice, likely a result of a lower number of precDC progenitor cells in this tissue. Taken together, our data suggest that the pluripotency-associated gene KLF4 is required for the maintenance of DCs in the spleen and consequently, survival of differentiated NK cells in this tissue.
authors.affiliation: Baylor College of Medicine, Texas Children's Hospital, 1102 Bates St., FC830.20, Houston, TX 77030, USA.
authors.forename: Chun Shik
authors.initials: CS
authors.lastname: Park
authors.forename: Ping-Hsien
authors.initials: PH
authors.lastname: Lee
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Audrea
authors.initials: A
authors.lastname: Burns
authors.forename: Ye
authors.initials: Y
authors.lastname: Shen
authors.forename: Monica
authors.initials: M
authors.lastname: Puppi
authors.forename: H Daniel
authors.initials: HD
authors.lastname: Lacorazza
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D016130:Immunophenotyping; D019426:Integrases / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D007371:Interferon-gamma; C045073:Cre recombinase; D019426:Integrases