Differential transcription of Eomes and T-bet during maturation of mouse uterine natural killer cells.
During human and rodent uterine decidualization, transient but abundant numbers of uterine natural killer (uNK) cells appear, proliferate, and differentiate. uNK cells share features with peripheral NK cells but are specialized to promote interferon-gamma (IFN-gamma)-mediated, pregnancy-associated, structural changes in maternal placental arteries. In CD8+ T cells and NK cells, the transcription factors T-bet and eomesodermin (Eomes) regulate maturation and effector functions, including IFN-gamma production. No studies are reported for uNK cells. Implantation sites in T-bet null mice, which have a defect in NK cell maturation, had uNK cells normal in morphology and number and normally modified spiral arteries. As Eomes null mice are not viable, real-time polymerase chain reaction comparisons between C57Bl/6J (B6) and alymphoid (Rag2(0/0)gammac0/0) mice were used to assess uNK cell expression of T-bet, Eomes, and the target genes IFN-gamma, granzyme A, and perforin. Gestation dated (gd) uterine tissues (mixed cell composition) and 200 morphologically homogeneous, laser-capture, microdissected uNK cells of different maturation stages were used. In uterus, Eomes transcripts greatly outnumbered those of T-bet, whether donors were nonpregnant or pregnant, and increased to gd10. In uNK cells, transcripts for T-bet, Eomes, and IFN-gamma were most abundant in mature stage cells, and transcripts for granzyme A and perforin were lower at this stage than in immature or senescent cells. Thus, Eomes dominance to T-bet discriminates regulation of the uNK cell subset from that observed for peripheral NK cells.
Tayade
Chandrakant
C
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1. ctayade@uoguelph.ca
Fang
Yuan
Y
Black
Gordon P
GP
V A
Paffaro
P
Erlebacher
Adrian
A
Croy
B Anne
BA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D030762:Estrous Cycle / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D053804:Granzymes; D007371:Interferon-gamma / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011247:Pregnancy; D050436:Regulatory Elements, Transcriptional / Q000235:genetics / Q000502:physiology; D012697:Serine Endopeptidases / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics; D014599:Uterus / Q000166:cytology / Q000276:immunology*; D000098815:T-bet Transcription Factor
C491198:Eomes protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human