Prolactin-like protein-A is a functional modulator of natural killer cells at the maternal-fetal interface.
Natural killer (NK) cells are the predominant lymphocytes present in healthy rodent and human implantation sites. In the rat, the expansion, differentiation and subsequent migration of NK cells away from the developing chorioallantoic placenta coincide with the expression of a novel pregnancy- and trophoblast cell-specific cytokine, prolactin (PRL)-like protein A (PLP-A). PLP-A specifically binds to uterine NK cells but does not appear to utilize receptor systems for PRL. In the present report, we show that PLP-A interactions with NK cells are not mediated by receptors utilized by known modulators of NK cell function, including interleukin-2, interleukin-7, interleukin-12, and interleukin-15 (IL-15). Uterine NK cells respond to PLP-A or IL-15 with an increase in intracellular calcium mobilization. In contrast, PLP-A, unlike IL-15, effectively suppresses the ability of NK cells to produce interferon-gamma (IFNgamma), a key mediator of NK cell function. Placental PLP-A expression is reciprocal to mesometrial decidua expression of IFNgamma. Increased expression of PLP-A by the placenta coincides with the decline of IFNgamma content in the mesometrial decidua adjacent to the placenta. In summary, trophoblast cell-derived PLP-A contributes to the regulation of NK cells at the maternal-fetal interface to ensure appropriate embryonic growth and development.
Ain
Rupasri
R
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Tash
Joseph S
JS
Soares
Michael J
MJ
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D003656:Decidua / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D019409:Interleukin-15 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014327:Trophoblasts / Q000378:metabolism
D019409:Interleukin-15; D007378:Interleukins; D011257:Pregnancy Proteins; C502143:Prl4a1 protein, rat; D007371:Interferon-gamma