Sostdc1 Regulates NK Cell Maturation and Cytotoxicity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Alberto J MillanJ O Manilay

Abstract

NK cells are innate-like lymphocytes that eliminate virally infected and cancerous cells, but the mechanisms that control NK cell development and cytotoxicity are incompletely understood. We identified roles for sclerostin domain-containing-1 (Sostdc1) in NK cell development and function. Sostdc1-knockout (Sostdc1-/-) mice display a progressive accumulation of transitional NK cells (tNKs) (CD27+CD11b+) with age, indicating a partial developmental block. The NK cell Ly49 repertoire in Sostdc1-/- mice is also changed. Lower frequencies of Sostdc1-/- splenic tNKs express inhibitory Ly49G2 receptors, but higher frequencies express activating Ly49H and Ly49D receptors. However, the frequencies of Ly49I+, G2+, H+, and D+ populations were universally decreased at the most mature (CD27-CD11b+) stage. We hypothesized that the Ly49 repertoire in Sostdc1-/- mice would correlate with NK killing ability and observed that Sostdc1-/- NK cells are hyporesponsive against MHC class I-deficient cell targets in vitro and in vivo, despite higher CD107a surface levels and similar IFN-γ expression to controls. Consistent with Sostdc1's known role in Wnt signaling regulation, Tcf7 and Lef1 levels were higher in Sostdc1-/- NK cells. Expression of the N...Continue Reading

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Citations

Dec 17, 2020·International Journal of Molecular Sciences·Ivy L DebreceniScott M Lieberman
Jan 27, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alberto J MillanJennifer O Manilay
Aug 21, 2021·Journal of Immunology Research·Xiaohu LiJinfeng Li

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