Identification and hormonal regulation of a novel form of NKp30 in human endometrial epithelium

Abstract

This study reports the discovery and steroid hormonal regulation of a novel glycosylated form of NKp30 in human endometrial epithelium. NKp30 is a member of the immunoglobulin superfamily and one of three existing natural cytotoxicity-triggering receptors. NKp30 is a glycosylated protein and is thought to be selectively expressed in resting and activated natural killer cells. The aims of the present study were to fully characterize NKp30 mRNA and protein in human endometrium during the menstrual cycle, and to investigate the hormonal regulation of NKp30. NKp30 mRNA was significantly up-regulated in fresh tissues during late secretory phase of the menstrual cycle. Interestingly, NKp30 mRNA was also present in clonally derived endometrial epithelial cells (CEE) in comparable amounts to fresh tissue. NKp30 protein was predominantly found in the endometrial glands and luminal epithelia of the secretory phase endometrium. Western blotting and de-glycosylation studies show that a novel glycosylated form of NKp30 is present in endometrial epithelium and that it can dimerize. Further phenotyping of CEE by flow cytometry revealed that they are CK8 + CD49f + NKp30 + CD45 -CD56 -. The data also show that transcription and translation of the novel form of NKp30 can be induced by progesterone treatment after 48 h in endometrial explants in vitro. This is the first report to show the presence of both NKp30 mRNA and a novel glycosylated form of NKp30 protein in endometrial epithelial cells.

The Stalk Domain and the Glycosylation Status of the Activating Natural Killer Cell Receptor NKp30 Are Important for Ligand Binding

“…In this context, we and others could show alterations in ligand binding of NKp30 from different (53). Along this line, it has already been shown that depending on the NKp30 isoform distinct signals are transmitted (48).…”

Natural cytotoxicity receptors and their ligands

“…The NKP30 gene which, like the NKP44 gene, is located in the class III region of the human MHC encodes a 30 kDa protein that is expressed on all mature NK cells 10 . In addition, NKp30 can be expressed on cord blood T cells after IL‐15 exposure, 32 on Vδ1 + T cells in presence of IL‐2 and IL‐15 upon TCR engagement, 33 as well as on endometrial epithelial cells after progesterone stimulation 34 . The NKp30 molecule is composed of one extracellular immunoglobulin domain.…”

B7-H6/NKp30 interaction: a mechanism of alerting NK cells against tumors

“…The intracellular tail of NKp30 has no signaling motif but its transmembrane domain associates via a charged amino acid with immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapters (CD3f and FcRc). NKp30 is mostly restricted to NK cells although recent studies have shown protein expression on umbilical cord blood T cells after IL-15 stimulation and on endometrial epithelial cells following progesterone exposure [17,18]. Moreover, the recently identified IL-22-producing mucosal innate lymphoid cell population that shares properties with LTi (lymphoid tissue inducer) and NK cells also expresses NKp30 [19,20].…”

“…In contrast NKp30c promotes IL-10 secretion, relaying an immunosuppressive signal through a rapid phosphorylation of p38 MAP kinase (see after for the reference). An additional layer of regulation could be provided by the existence of several glycosylation profiles of NKp30 [17]. At present, these important issues have to be unveiled.…”