title: Abundant stage-dependent Ly49E expression by liver NK cells is not essential for their differentiation and function.
abstract: The NKR Ly49E has several unique characteristics. Unlike most NKRs, Ly49E is highly expressed on fetal NK cells, whereas expression is decreased on bone marrow-derived NK cells in adult mice. To investigate a possible role for Ly49E in NK cell differentiation and function, we have generated an Ly49E KO mouse. Our results show that bone marrow and splenic NK cells are present in normal numbers in Ly49E KO mice, expressing an unaltered panel of NKRs and differentiation markers. Furthermore, cytokine production and cytotoxicity by these cells are unaffected. Surprisingly, WT DX5(-) liver NK cells express high Ly49E levels in fetal and adult mice. Ly49E(+)DX5(-) liver NK cells transferred into Rag-2(-/-)/gc(-/-) mice maintain high Ly49E expression in the liver and differentiate into DX5(+) NK cells in spleen and bone marrow. Ly49E expression is not crucial for liver NK cell differentiation during ontogeny, as the DX5(-)/DX5(+) ratio, the NKR repertoire, and the granzyme B and TRAIL levels are comparable in Ly49E KO versus WT mice, except for lower TRAIL expression on DX5(-) liver NK cells in 20-day-old mice. The TRAIL-, perforin-, and FasL-mediated cytolysis by liver NK cells is unaffected in Ly49E KO mice. Collectively, we show that in addition to high Ly49E expression on fetal NK cells versus low Ly49E expression on conventional NK cells in adult life, Ly49E remains highly expressed on DX5(-) liver NK cells. However, Ly49E expression does not have a crucial role in differentiation and/or function of these NK cells.
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Filtjens
authors.forename: Sylvie
authors.initials: S
authors.lastname: Taveirne
authors.forename: Aline
authors.initials: A
authors.lastname: Van Acker
authors.forename: Els
authors.initials: E
authors.lastname: Van Ammel
authors.forename: Mandy
authors.initials: M
authors.lastname: Vanhees
authors.forename: Tessa
authors.initials: T
authors.lastname: Kerre
authors.forename: Tom
authors.initials: T
authors.lastname: Taghon
authors.forename: Bart
authors.initials: B
authors.lastname: Vandekerckhove
authors.forename: Jean
authors.initials: J
authors.lastname: Plum
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation; D053804:Granzymes / Q000032:analysis; D039421:Integrin alpha2 / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis
chemical_list: D039421:Integrin alpha2; C527093:Klra5 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; D053221:TNF-Related Apoptosis-Inducing Ligand; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse