Kruppel-like factor 4 (KLF4) promotes the survival of natural killer cells and maintains the number of conventional dendritic cells in the spleen.

Journal of Leukocyte Biology
Chun Shik ParkH Daniel Lacorazza

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 ...Continue Reading

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Citations

Nov 20, 2012·Nature Immunology·Ansuman T SatpathyKenneth M Murphy
Oct 1, 2013·Immunology Letters·Maksim MamonkinH Daniel Lacorazza
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Jun 21, 2020·Cancers·Dandan Wang, Subramaniam Malarkannan
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Mar 5, 2021·Oncotarget·Andrew Henry LewisH Daniel Lacorazza
Jan 23, 2021·Annual Review of Immunology·Mar Cabeza-CabrerizoCaetano Reis E Sousa

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