Interactions between uterine natural killer cells and progesterone, estrogen, and human chorionic gonadotropin. (WP5569)

Homo sapiens

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Immunometabolism at maternal-fetal interface: interactions between the hormones progesterone (P4), estrogen (estradiol, E2), and human chorionic gonadotropin (hCG) and uterine nk cells (uNK). This model represents the secretory phase of the menstrual cycle and first trimester period of pregnancy for these interactions.

For a description of pathway objects, see the WikiPathways Legend.

Authors

AyoubElHabchi and Denise Slenter

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Disease Ontology

immune system disease

Pathway Ontology

chemokine mediated signaling pathway immune response pathway integrin mediated signaling pathway Jak-Stat signaling pathway cytokine mediated signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Estradiol Metabolite chebi:23965
Progesterone Metabolite chebi:17026
Estrogen Metabolite chebi:50114
hCG Metabolite wikidata:Q407172
CCL7 GeneProduct ensembl:ENSG00000108688
CCL5 GeneProduct ensembl:ENSG00000271503
BCL2 Protein uniprot:P10415
MAPK11 Protein uniprot:Q15759
CX3CL1 Protein uniprot:P78423
CXCL12 Protein uniprot:P48061
CCL3 Protein uniprot:P10147
CCL8 Protein uniprot:P80075
MAPK3 Protein uniprot:P27361
GAB3 Protein uniprot:Q8WWW8
JAK3 Protein uniprot:P52333
STAT5A Protein uniprot:P42229
CCL4 Protein uniprot:P13236
MAP2K4 Protein uniprot:P45985
ANGPT1 Protein uniprot:Q15389
JAK1 Protein uniprot:P23458
ANGPT2 Protein uniprot:O15123
CXCR4 Protein uniprot:P61073
MRC1 Protein uniprot:P22897
KIR2DL4 Protein uniprot:Q99706
CXCL10 Protein uniprot:P02778
CXCL8 Protein uniprot:P10145
VEGFA Protein uniprot:P15692
ESR2 Protein uniprot:Q92731
CCL2 Protein uniprot:P13500
IL3 Protein uniprot:P08700
IL-6 Protein uniprot:P05231
IL-15 Protein uniprot:P40933
HLA-G Protein uniprot:P17693
CXCL11 Protein uniprot:O14625
PGR Protein uniprot:P06401
Nkp30 Protein uniprot:O14931
GR Protein uniprot:P04150
Nkp44 Protein uniprot:O95944
Nkp46 Protein uniprot:O76036
IFN-γ Protein uniprot:P01579
CD69 Protein uniprot:Q07108
α4-integrin Protein uniprot:P13612
L-selectin Protein uniprot:P14151
CXCR3 Protein uniprot:P49682
GATA2 Protein uniprot:P23769
TNF Protein uniprot:P01375
PIBF1 Protein uniprot:Q8WXW3
IL10 Protein uniprot:P22301
IL4 Protein uniprot:P05112
STAT5B Protein uniprot:P51692
MCL1 Protein uniprot:Q07820
γc Protein uniprot:P31785
IL2RB Protein uniprot:P14784
IL15RA Protein uniprot:Q13261
MADCAM1 Protein uniprot:Q13477
VCAM1 Protein uniprot:P19320

References

  1. Effect of female sex steroids on human endometrial CD16neg CD56bright natural killer cells. Kitaya K, Yasuda J, Nakayama T, Fushiki S, Honjo H. Fertil Steril. 2003 Mar;79 Suppl 1:730–4. PubMed Europe PMC Scholia
  2. Recruitment of uterine NK cells: induction of CXC chemokine ligands 10 and 11 in human endometrium by estradiol and progesterone. Sentman CL, Meadows SK, Wira CR, Eriksson M. J Immunol. 2004 Dec 1;173(11):6760–6. PubMed Europe PMC Scholia
  3. Trafficking of peripheral blood CD56(bright) cells to the decidualizing uterus--new tricks for old dogmas? van den Heuvel M, Peralta C, Bashar S, Taylor S, Horrocks J, Croy BA. J Reprod Immunol. 2005 Oct;67(1–2):21–34. PubMed Europe PMC Scholia
  4. Trafficking of circulating pro-NK cells to the decidualizing uterus: regulatory mechanisms in the mouse and human. van den Heuvel MJ, Chantakru S, Xuemei X, Evans SS, Tekpetey F, Mote PA, et al. Immunol Invest. 2005;34(3):273–93. PubMed Europe PMC Scholia
  5. Osteopontin expression in human decidua is associated with decidual natural killer cells recruitment and regulated by progesterone. Qu X, Yang M, Zhang W, Liang L, Yang Y, Zhang Y, et al. In Vivo. 2008;22(1):55–61. PubMed Europe PMC Scholia
  6. Glucocorticoid receptor mediates the effect of progesterone on uterine natural killer cells. Guo W, Li P, Zhao G, Fan H, Hu Y, Hou Y. Am J Reprod Immunol. 2012 Jun;67(6):463–73. PubMed Europe PMC Scholia
  7. Estrogen-dependent regulation of human uterine natural killer cells promotes vascular remodelling via secretion of CCL2. Gibson DA, Greaves E, Critchley HOD, Saunders PTK. Hum Reprod. 2015 Jun;30(6):1290–301. PubMed Europe PMC Scholia
  8. HLA-G Orchestrates the Early Interaction of Human Trophoblasts with the Maternal Niche. Gregori S, Amodio G, Quattrone F, Panina-Bordignon P. Front Immunol. 2015 Mar 30;6:128. PubMed Europe PMC Scholia
  9. The regulation of ovary and conceptus on the uterine natural killer cells during early pregnancy. Gong H, Chen Y, Xu J, Xie X, Yu D, Yang B, et al. Reprod Biol Endocrinol. 2017 Sep 6;15(1):73. PubMed Europe PMC Scholia
  10. The Role of Extracellular Vesicles and PIBF in Embryo-Maternal Immune-Interactions. Szekeres-Bartho J, Šućurović S, Mulac-Jeričević B. Front Immunol. 2018 Dec 13;9:2890. PubMed Europe PMC Scholia
  11. Human Chorionic Gonadotropin-Mediated Immune Responses That Facilitate Embryo Implantation and Placentation. Schumacher A, Zenclussen AC. Front Immunol. 2019 Dec 10;10:2896. PubMed Europe PMC Scholia
  12. Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development. Wang X, Zhao XY. Front Immunol. 2021 Mar 18;12:610789. PubMed Europe PMC Scholia
  13. Biology and pathology of the uterine microenvironment and its natural killer cells. Wang F, Qualls AE, Marques-Fernandez L, Colucci F. Cell Mol Immunol. 2021 Sep;18(9):2101–13. PubMed Europe PMC Scholia
  14. Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications. Zhang X, Wei H. Front Immunol. 2021 Aug 26;12:728291. PubMed Europe PMC Scholia
  15. Interleukin-15 in Outcomes of Pregnancy. Gordon SM. Int J Mol Sci. 2021 Oct 14;22(20):11094. PubMed Europe PMC Scholia
  16. Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation. Xie M, Li Y, Meng YZ, Xu P, Yang YG, Dong S, et al. Front Immunol. 2022 Jun 1;13:918550. PubMed Europe PMC Scholia
  17. The effects of progesterone on immune cellular function at the maternal-fetal interface and in maternal circulation. Motomura K, Miller D, Galaz J, Liu TN, Romero R, Gomez-Lopez N. J Steroid Biochem Mol Biol. 2023 May;229:106254. PubMed Europe PMC Scholia
  18. Cytokine modulation and immunoregulation of uterine NK cells in pregnancy disorders. Zhou J, Yan P, Ma W, Li J. Cytokine Growth Factor Rev. 2025 Feb;81:40–53. PubMed Europe PMC Scholia