Sostdc1 Regulates NK Cell Maturation and Cytotoxicity.
| Autor: | Millan AJ; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and., Elizaldi SR; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and., Lee EM; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and., Aceves JO; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and., Murugesh D; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and., Loots GG; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and.; Physical and Life Sciences Directorate, Lawrence Livermore National Laboratories, Livermore, CA 94550., Manilay JO; Department of Molecular Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA 95343; and jmanilay@ucmerced.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Apr 15; Vol. 202 (8), pp. 2296-2306. Date of Electronic Publication: 2019 Feb 27. |
| DOI: | 10.4049/jimmunol.1801157 |
| Abstrakt: | 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 NK development gene Id2 was decreased in Sostdc1 -/- immature NK and tNK cells, but Eomes and Tbx21 expression was unaffected. Reciprocal bone marrow transplant experiments showed that Sostdc1 regulates NK cell maturation and expression of Ly49 receptors in a cell-extrinsic fashion from both nonhematopoietic and hematopoietic sources. Taken together, these data support a role for Sostdc1 in the regulation of NK cell maturation and cytotoxicity, and identify potential NK cell niches. (Copyright © 2019 by The American Association of Immunologists, Inc.) |
| Databáze: | MEDLINE |
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