Killer cell immunoglobulin-like receptors and human leukocyte antigen C pathway (WP5576)

Homo sapiens

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The relationship between killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells and human leukocyte antigen C (HLA-C) molecules on trophoblast cells during pregnancy.

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

Authors

Johidi Rog , Alex Pico , and Egon Willighagen

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Cell Type Ontology

natural killer cell

Pathway Ontology

signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
CD34 GeneProduct hgnc.symbol:CD34 CD34(+) cell present in the endometrium or decidua
HLA-C Protein uniprot:P10321
GM-CSF Protein uniprot:P04141 Supports trophoblast growth and vascular remodeling enhancing placentation
Transcriptome profiling via microarray
DAG Protein uniprot:P17252
SLP-76 Protein uniprot:Q13094
IFN-γ Protein uniprot:P01579 Robustly produced following activating KIR engagement.
IFN-γ inhibits trophoblast invasion by inducing apoptosis and suppressing protease activity
Transcriptome profiling via microarray
Syk Protein uniprot:P43405
Ras Protein uniprot:P01112
PLC-γ1 Protein uniprot:P19174
VAV1 Protein uniprot:P15498
SHP-1 Protein uniprot:P29350
SHP-2 Protein uniprot:P17706
PKC Protein uniprot:Q04759
TNF-α Protein uniprot:P01375 Via its action on endometrial stromal cells, TNF-α can also indirectly promote trophoblast invasion by creating a supportive inflammatory environment
Elevated TNF-α impairs trophoblast migration and invasion
This duality highlights the importance of tightly regulated TNF-α signaling for successful implantation and placental development
KIR2DL1 Protein uniprot:P43626 Cytoplasmic tail contains ITIM motif
Grb2 Protein uniprot:P62993
FYN Protein uniprot:P06241
LAT Protein uniprot:O43561
RAC1 Protein uniprot:P63000
IP3 Protein uniprot:Q14643
DAP12 Protein uniprot:O43914 Contains immunoreceptor tyrosine-based activation motif (ITAM)
KIR2DL2 Protein uniprot:P43627
KIR2DS1 Protein uniprot:Q14954
KIR2DL3 Protein uniprot:P43628
IFN-γ Protein uniprot:P01579 Robustly produced following activating KIR engagement; critical for immune modulation and trophoblast invasion

References

  1. Association of supervillin with KIR2DL1 regulates the inhibitory signaling of natural killer cells. Liu HP, Yu MC, Jiang MH, Chen JX, Yan DP, Liu F, et al. Cell Signal. 2011 Feb;23(2):487–96. PubMed Europe PMC Scholia
  2. Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells. Kim HS, Long EO. Sci Signal. 2012 Jul 10;5(232):ra49. PubMed Europe PMC Scholia
  3. Immunoreceptor tyrosine-based inhibitory motif (ITIM)-mediated inhibitory signaling is regulated by sequential phosphorylation mediated by distinct nonreceptor tyrosine kinases: a case study involving PECAM-1. Tourdot BE, Brenner MK, Keough KC, Holyst T, Newman PJ, Newman DK. Biochemistry. 2013 Apr 16;52(15):2597–608. PubMed Europe PMC Scholia
  4. Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation. Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, et al. J Clin Invest. 2013 Oct;123(10):4264–72. PubMed Europe PMC Scholia
  5. Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation. Xiong S, Sharkey AM, Kennedy PR, Gardner L, Farrell LE, Chazara O, et al. J Clin Invest. 2013 Oct;123(10):4264–72. PubMed Europe PMC Scholia
  6. Vascular Endothelial Growth Factor-A (VEGF-A) Mediates Activin A-Induced Human Trophoblast Endothelial-Like Tube Formation. Li Y, Zhu H, Klausen C, Peng B, Leung PCK. Endocrinology. 2015 Nov;156(11):4257–68. PubMed Europe PMC Scholia
  7. KIR2DL3 and KIR2DL1 show similar impact on licensing of human NK cells. Sim MJW, Stowell J, Sergeant R, Altmann DM, Long EO, Boyton RJ. Eur J Immunol. 2016 Jan;46(1):185–91. PubMed Europe PMC Scholia
  8. Expression of KIR2DS1 by decidual natural killer cells increases their ability to control placental HCMV infection. Crespo ÂC, Strominger JL, Tilburgs T. Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15072–7. PubMed Europe PMC Scholia
  9. Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1. Matalon O, Ben-Shmuel A, Kivelevitz J, Sabag B, Fried S, Joseph N, et al. EMBO J. 2018 Mar 1;37(5):e96264. PubMed Europe PMC Scholia
  10. Natural killer cell cytotoxicity and its regulation by inhibitory receptors. Kumar S. Immunology. 2018 Jul;154(3):383–93. PubMed Europe PMC Scholia
  11. Increased expression of IFN-γ in preeclampsia impairs human trophoblast invasion via a SOCS1/JAK/STAT1 feedback loop. Liu H, Wang W, Liu C. Exp Ther Med. 2021 Feb;21(2):112. PubMed Europe PMC Scholia
  12. Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors. Rettman P, Blunt MD, Fulton RJ, Vallejo AF, Bastidas-Legarda LY, España-Serrano L, et al. J Immunother Cancer. 2021 May;9(5):e001912. PubMed Europe PMC Scholia
  13. High Levels of Tumor Necrosis Factor-Alpha Reduce Placental Aquaporin 3 Expression and Impair in vitro Trophoblastic Cell Migration. Dos Passos Junior RR, de Freitas RA, Reppetti J, Medina Y, Dela Justina V, Bach CW, et al. Front Physiol. 2021 Jun 29;12:696495. PubMed Europe PMC Scholia
  14. Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation. Fionda C, Stabile H, Molfetta R, Kosta A, Peruzzi G, Ruggeri S, et al. Eur J Immunol. 2021 Nov;51(11):2607–17. PubMed Europe PMC Scholia
  15. TNF-α Regulated Endometrial Stroma Secretome Promotes Trophoblast Invasion. You Y, Stelzl P, Joseph DN, Aldo PB, Maxwell AJ, Dekel N, et al. Front Immunol. 2021 Nov 1;12:737401. PubMed Europe PMC Scholia
  16. Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health. Pollock NR, Harrison GF, Norman PJ. J Allergy Clin Immunol Pract. 2022 Jul;10(7):1763–75. PubMed Europe PMC Scholia