Decidual Cell Regulation of Natural Killer Cell–Recruiting Chemokines
| Autor: | Jie Xu, Yingqun Huang, S. Joseph Huang, Saeed Faramarzi, Frederick Schatz, Charles J. Lockwood, Louise A. Koopman, Chie-Pein Chen, Umit A. Kayisli, Lynn Buchwalder, Dineke H P M Smedts, Ozlem kayisli |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
0303 health sciences
Chemokine 030219 obstetrics & reproductive medicine Monocyte Decidua Biology CXCR3 Natural killer cell Pathology and Forensic Medicine Andrology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immunology medicine biology.protein Interferon gamma Decidual cells Tumor necrosis factor alpha 030304 developmental biology medicine.drug |
| Zdroj: | The American Journal of Pathology. 183(3):841-856 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2013.05.029 |
| Popis: | First trimester human decidua is composed of decidual cells, CD56brightCD16− decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated with NK cell–derived IFN-γ and either macrophage-derived TNF-α or IL-1β synergistically enhanced mRNA and protein expression of IP-10 and I-TAC. Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN-γ receptor 1 and 2 mediation via JAK/STAT and NFκB signaling pathways. However, synergy was not observed on neutrophil, monocyte, and NK cell–recruiting chemokines. Immunostaining of first trimester decidua localized IP-10, I-TAC, IFN-γR1, and -R2 to vimentin-positive decidual cells versus cytokeratin-positive interstitial trophoblasts. Flow cytometry identified high CXCR3 levels on dNK cells and minority peripheral CD56brightCD16− pNK cells and intermediate CXCR3 levels on the majority of CD56dimCD16+ pNK cells. Incubation of pNK cells with either IP-10 or I-TAC elicited concentration-dependent enhanced CXCR3 levels and migration of both pNK cell subsets that peaked at 10 ng/mL, whereas each chemokine at a concentration of 50 ng/mL inhibited CXCR3 expression and pNK cell migration. Deciduae from women with preeclampsia, a leading cause of maternal and fetal morbidity and mortality, displayed significantly lower dNK cell numbers and higher IP-10 and I-TAC levels versus gestational age–matched controls. Significantly elevated IP-10 levels in first trimester sera from women eventually developing preeclampsia compared with controls, identifying IP-10 as a novel, robust early predictor of preeclampsia. |
| Databáze: | OpenAIRE |
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