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

• DOI: 10.1189/jlb.0811413
• Publication Date: 2012-02-18T04:42:31Z
• Authors: Chun Shik Park; Ping-Hsien Lee; Takeshi Yamada; Audrea Burns; Ye Shen; Monica Puppi; H Daniel Lacorazza
• Keywords: Male; Mice, Knockout; 0301 basic medicine; Integrases; Blotting, Western; Kruppel-Like Transcription Factors; Apoptosis; Cell Differentiation; Mice, Transgenic; Dendritic Cells; Flow Cytometry; Immunophenotyping; Killer Cells, Natural; Mice, Inbred C57BL; Interferon-gamma; Kruppel-Like Factor 4; Mice; 03 medical and health sciences; Animals; Female; RNA, Messenger; Bone Marrow Transplantation

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 CD11chi 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.