Tissue-resident natural killer cells: features of functioning in the uterus and decidual membrane
Abstract
Natural killers are a heterogeneous population of innate immune lymphocytes, among which in recent years 2 categories of cells have been distinguished - circulating (cNK) and tissue-resident (trNK). The circulating pool of these cells is now fairly well characterized: these are cells of bone marrow origin with predominantly cytolytic activity, predominanly CD56dimCD16+ phenotype and a high level of perforin and granzymes expression. The tissue-resident pool has not yet been sufficiently studied, but a number of its features have been established: the ability to differentiate in tissues, the predominance of the CD56brightCD16- phenotype, the ability to produce high levels of certain regulatory cytokines (IFN-γ, TNFα, GM-CSF), the nature of the expression of receptors specific to class I histocompatibility molecules, etc. One of the most important features of trNKs is that their properties correspond to the specific organ where they are localized. This review is devoted to the characteristics of the natural killer cells of the uterus (uNK) and the decidual membrane (dNK) during pregnancy, the features of their origin, phenotype, cytokine production and the set of implemented functions.
Keywords:natural killer cells; circulating NK cells; tissue-resident NK cells; uterine NK cells; decidual NK cells; immunology of reproduction
For citation: Khamatova A.A., Chebotareva T.A., Balmasova I.P Tissue-resident natural killer cells: features of functioning in the uterus and decidual membrane. Immunologiya. 2021; 42 (5): 574-80. DOI: https://doi.org/10.33029/0206-4952-2021-42-5-574-580 (in Russian)
Funding. The study had no sponsor support.
Conflict of interests. The authors declare no conflict of interests.
References
1. Hashemi E., Malarkannan S. Tissue-resident NK cells: development, maturation, and clinical relevance. Cancers (Basel). 2020; 12 (6): 1553. DOI: https://doi.org/10.3390/cancers12061553
2. Erlebacher A. Immunology of the maternal-fetal interface. Annu. Rev. Immunol. 2013; 31: 387–411. DOI: https://doi.org/10.1146/annurev-immunol-032712-100003
3. Vacca P., Vitale C., Munari E., Cassatella M.A., Mingari M.C., Moretta L. Human innate lymphoid cells: Their functional and cellular interactions in decidua. Front. Immunol. 2018; 9: 1897. DOI: https://doi.org/10.3389/fimmu.2018.01897
4. Saito S., Nakashima A., Shima T., Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am. J. Reprod. Immunol. 2010; 63 (6): 601–10. DOI: https://doi.org/10.1111/j.1600-0897.2010.00852.x
5. Mor G., Cardenas I., Abrahams V., Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann. N. Y. Acad. Sci. 2011; 1221: 80–7. DOI: https://doi.org/10.1111/j.1749-6632.2010.05938.x
6. Aluvihare V.R., Kallikourdis M., Betz A.G. Regulatory T cells mediate maternal tolerance to the fetus. Nat. Immunol. 2004; 5 (3): 266–71. DOI: https://doi.org/10.1038/ni1037
7. Björkström N.K. Ljunggren H.G. Michaëlsson J. Emerging insights into natural killer cells in human peripheral tissues. Nat. Rev. Immunol. 2016; 16(5): 310–20. DOI: https://doi.org/10.1038/nri.2016.34
8. Klose C.S., Artis D. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat. Immunol. 2016; 17 (7): 765–74. DOI: https://doi.org/10.1038/ni.3489
9. Sun H., Sun C., Xiao W., Sun R. Tissue-resident lymphocytes: from adaptive to innate immunity. Cell. Mol. Immunol. 2019; 16(3): 205–15. DOI: https://doi.org/10.1038/s41423-018-0192-y
10. Cherrier M., Ohnmacht C., Cording S., Eberl G. Development and function of intestinal innate lymphoid cells. Curr. Opin. Immunol. 2012; 24 (3): 277–83. DOI: https://doi.org/10.1016/j.coi.2012.03.011
11. Monticelli L.A., Sonnenberg G.F., Abt M.C., Alenghat T., Ziegler C.G., Doering T.A., Angelosanto J.M., Laidlaw B.J., Yang C.Y., Sathaliyawala T., Kubota M., Turner D., Diamond J.M., Goldrath A.W., Farber D.L., Collman R.G., Wherry E.J., Artis D. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat. Immunol. 2011; 12 (11): 1045–54. DOI: https://doi.org/10.1031/ni.2131
12. Liu S., Diao L., Huang C., Li Y., Zeng Y., Kwak-Kim J.Y.H. The role of decidual immune cells on human pregnancy. J. Reprod. Immunol. 2017; 124: 44–53. DOI: https://doi.org/10.1016/j.jri.2017.10.045
13. Negishi Y., Takahashi H., Kuwabara Y., Takeshita T. Innate immune cells in reproduction. J. Obstet. Gynaecol. Res. 2018; 44 (11): 2025–36. DOI: https://doi.org/10.1111/jog.13759
14. Koch J., Steinle A., Watzl C., Mandelboim O. Activating natural cytotoxicity receptors of natural killer cells in cancer and infection. Trends Immunol. 2013; 34 (4): 182–91. DOI: https://doi.org/10.1016/j.it.2013.01.003
15. Гудима О.Г., Хаитов Р.М. Клеточный иммунитет при ВИЧ-инфекции. Физиология и патология иммунной системы. 2018; 22 (12): 3–45. [Gudima G.O., Khaitov R.M. Cellular immunity and HIV infection. Physiology and pathology of the immune system. 2018; 22 (12): 3–45. (in Russian)]
16. Topham N.J., Hewitt E.W. Natural killer cell cytotoxicity: how do they pull the trigger? Immunology. 2009; 128 (1): 7–15. DOI: https://doi.org/10.1111/j.1365-2567.2009.03123.x
17. Duensing T.D., Watson S.R. Assesment of antibody-dependent cellular cytotoxicity by flow cytometry. Cold Spring Harb. Protoc. 2018; 2018 (2). DOI: https://doi.org/10.1101/pdb.prot093815
18. Mody C.H., Ogbomo H., Xiang R.F., Kyei S.K., Feehan D., Islam A., Li S.S. Microbial killing by NK cells. J. Leukoc. Biol. 2019; 105 (6): 1285–96. DOI: https://doi.org/10.1002/JLB.MR0718-298R
19. Waggoner S.N., Cornberg M., Selin L.K., Welsh R.M. Natural killer cells act as rheostats modulating antiviral T cells. Nature. 2011; 481 (7381): 394–8. DOI: https://doi.org/10.1038/nature10624
20. Bruno A., Mortara L., Baci D., Noonan D.M., Albini A. Myeloid derived suppressor cells interactions with Natural Killer cells and pro-angiogenic activities: roles in tumor progression. Front. Immunol. 2019; 10: 771. DOI: https://doi.org/10.3389/fimmu.2019.00771
21. Vivier E., Tomasello E., Baratin M., Walzer T., Ugolini S. Functions of natural killer cells. Nat. Immunol. 2008; 9 (5): 503–10. DOI: https://doi.org/10.1038/ni1582
22. Carrega P., Bonaccorsi I., Di Carlo E., Morandi B., Paul P., Rizzello V., Cipollone G., Navarra G., Mingari M.C., Moretta L., Ferlazzo G. CD56(bright)perforin(low) noncytotoxic human NK cells are abundant in both healthy and neoplastic solid tissues and recirculate to secondary lymphoid organs via afferent lymph. J. Immunol. 2014; 192 (8): 3805–15. DOI: https://doi.org/10.4049/jimmunol.1301889
23. Faas M.M., De Vos P. Uterine NK cells and macrophages in pregnancy. Placenta. 2017; 56: 44–52. DOI: https://doi.org/10.1016/j.placenta.2017.03.001
24. Wang R., Jaw J.J., Stutzman N.C., Zou Z., Sun P.D.J. Natural killer cell-produced IFN-γ and TNF-α induce target cell cytolysis through up-regulation of ICAM-1. J. Leukoc. Biol. 2012; 91: 299–309. DOI: https://doi.org/10.1189/jlb.0611308
25. Sojka D.K., Plougastel-Douglas B., Yang L., Pak-Wittel M.A., Artyomov M.N., Ivanova Y., Zhong C., Chase J.M., Rothman P.B., Yu J.J. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. eLife. 2014; 3: e01659. DOI: https://doi.org/10.7554/eLife.01659
26. Huntington N.D., Legrand N., Alves N.L., Jaron B., Weijer K., Plet A., Corcuff E., Mortier E., Jacques Y., Spits H. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J. Exp. Med. 2009; 206 (1): 25–34. DOI: https://doi.org/10.1084/jem.20082013
27. Abel A.M., Yang C., Thakar M.S., Malarkannan S. Natural killer cells: Development, maturation, and clinical utilization. Front. Immunol. 2018; 9: 1869. DOI: https://doi.org/10.3389/fimmu.2018.01869
28. Salzberger W., Martrus G., Bachmann K., Goebels H., Heß L., Koch M., Langeneckert A., Lunemann S., Oldhafer K.J., Pfeifer C. Tissue-resident NK cells differ in their expression profile of the nutrient transporters Glut1, CD98 and CD71. PLoS One. 2018; 13 (7): e0201170. DOI: https://doi.org/10.1371/journal.pone.0201170
29. Hesslein D.G.T., Lanier L.L. Transcriptional control of natural killer cell development and function. Adv. Immunol. 2011; 109: 45–85. DOI: https://doi.org/10.1016/B978-0-12-387664-5.00002-9
30. Daussy C., Faure F., Mayol K., Viel S., Gasteiger G., Charrier E., Bienvenu J., Henry T., Debien E., Hasan U.A., Marvel J., Yoh K., Takahashi S., Prinz I., de Bernard S., Buffat L., Walzer T. T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow. J. Exp. Med. 2014; 211 (3): 563–77. DOI: https://doi.org/10.1084/jem.20131560
31. Male V., Nisoli I., Kostrzewski T., Allan D.S.J., Carlyle J.R., Lord G.M., Wack A., Brady H.J.M. The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression. J. Exp. Med. 2014; 211 (4): 635–42. DOI: https://doi.org/10.1084/jem.20132398
32. Rajasekaran K., Riese M.J., Rao S., Wang L., Thakar M.S., Sentman C.L., Malarkannan S. Signaling in effector lymphocytes: Insights toward safer immunotherapy. Front. Immunol. 2016; 7: 176. DOI: https://doi.org/10.3389/fimmu.2016.00176
33. Diefenbach A., Jamieson A.M., Liu S.D., Shastri N., Raulet D.H. Ligands for the murine NKG2D receptor: Expression by tumor cells and activation of NK cells and macrophages. Nat. Immunol. 2000; 1 (2): 119–26. DOI: https://doi.org/10.1038/77793
34. Kumar S. Natural killer cell cytotoxicity and its regulation by inhibitory receptors. Immunology. 2018; 154 (3): 383–93. DOI: https://doi.org/10.1111/imm.12921
35. Marquardt N., Vivien Beziat V., Nystrom S., Hengst J., Ivarsson M.A., Kekalainen E., Johansson H., Mjosberg J., Westgren M., Lankisch T.O., Wedemeyer H., Ellis E.C., Ljunggren H.G., Michaelsson J., Bjorkstrom N.K. Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells. J. Immunol. 2015; 194: 2467–71. DOI: https://doi.org/10.4049/jimmunol.1402756
36. Sharkey A.M., Xiong S., Kennedy P.R., Gardner L., Farrell L.E., Chazara O., Ivarsson M.A., Hiby S.E., Colucci F., Moffett A. Tissue-specific education of decidual NK cells. J. Immunol. 2015; 195 (7): 3026–32. DOI: https://doi.org/10.4049/jimmunol.1501229
37. Lanier L.L. NKG2D receptor and its ligands in host defense. Cancer Immunol. Res. 2015; 3 (6): 575–82. DOI: https://doi.org/10.1158/2326-6066.CIR-15-0098
38. Kruse P.H., Matta J., Ugolini S., Vivier E. Natural cytotoxicity receptors and their ligands. Immunol. Cell Biol. 2014; 92 (3): 221–9. DOI: https://doi.org/10.1038/icb.2013.98
39. Huhn O., Ivarsson M.A., Gardner L., Hollinshead M., Stinchcombe J.C., Chen P., Shreeve N., Chazara O., Farrell L.E., Theorell J., Ghadially H., Parham P., Griffiths G., Horowitz A., Moffett A., Sharkey A.M., Colucci F. Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy. Nat. Commun. 2020; 11 (1): 381. DOI: https://doi.org/10.1038/s41467-019-14123-z
40. Gamliel M., Goldman-Wohl D., Isaacson B., Gur C., Stein N., Yamin R., Berger M., Grunewald M., Keshet E., Rais Y., Bornstein Ch., David E., Jelinski A., Eisenberg I., Greenfield C., Ben-David A., Imbar T., Gilad R., Haimov-Kochman R., Mankuta D., Elami-Suzin M., Amit I., Hanna J.H., Simcha Yagel S., Mandelboim O. Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity. 2018; 48 (5): 951–62. DOI: https://doi.org/10.1016/j.immuni.2018.03.030
41. Brosens I., Pijnenborg R., Vercruysse L., Romero R. The «Great Obstetrical Syndromes» are associated with disorders of deep placentation. Am. J. Obstet. Gynecol. 2011; 204 (3): 193–201. DOI: https://doi.org/10.1016/j.ajog.2010.08.009
42. Kwan M., HazanA., Zhang J., Jones R.L., Harris L.K., Whittle W., Keating S., Dunk C.E., Lye S.J. Dynamic changes in maternal decidual leukocyte populations from first to second trimester gestation. Placenta. 2014; 35 (12): 1027–34. DOI: https://doi.org/10.1016/j.placenta.2014.09.018
43. Moffett-King А. Natural killer cells and pregnancy. Nat. Rev. Immunol. 2002; 2 (9): 656–63. DOI: https://doi.org/10.1038/nri886
44. Hanna J., Goldman-Wohl D., Hamani Y.,Avraham I., Greenfield C., Natanson-Yaron S., Prus D., Cohen-Daniel L., Arnon T.I., Manaster I., Gazit R., Yutkin V., Benharroch D., Porgador A., Keshet E., Yagel S., Mandelboim O. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat. Med. 2006; 12 (9): 1065–74. DOI: https://doi.org/10.1038/nm1452
45. Helige C., Ahammer H., Moser G., Hammer A., Dohr G., Huppertz B., Sedlmayr P. Distribution of decidual natural killer cells and macrophages in the neighbourhood of the trophoblast invasion front: a quantitative evaluation. Hum. Reprod. 2014; 29 (1): 8–17. DOI: https://doi.org/10.1093/humrep/det353
46. Vacca P., Cantoni C., Prato C., Fulcheri E., Moretta A., Moretta L., Mingari M.C. Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells. Int. Immunol. 2008; 20 (11): 1395–405. DOI: https://doi.org/10.1093/intimm/dxn105
47. Vacca P., Vitale C., Montaldo E., Conte R., Cantoni C., Fulcheri E., Darretta V., Moretta L., Mingari M.C. CD34+ hematopoietic precursors are present in human decidua and differentiate into natural killer cells upon interaction with stromal cells. Proc. Natl Acad. Sci. USA. 2011; 108 (6): 2402–7. DOI: https://doi.org/10.1073/pnas.1016257108
48. Male V., Hughes T., McClory S., Colucci F., Caligiuri M.A., Moffett A. Immature NK cells, capable of producing il-22, are present in human uterine mucosa. J. Immunol. 2010; 185 (7): 3913–8. DOI: https://doi.org/10.4049/jimmunol.1001637
49. Tao Y., Li Y.-H., Piao H.-L., Zhou W.-J., Zhang D., Fu Q., Wang S.-C., Li D.-J., Du M.-R. CD56(bright)CD25+ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy. Cell. Mol. Immunol. 2015; 12(1): 77–86. DOI: https://doi.org/10.1038/cmi.2014.26
50. Vacca, P., Moretta L., Moretta A., Mingari M.C. Origin, phenotype and function of human natural killer cells in pregnancy. Trends Immunol. 2011; 32 (11): 517–23. DOI: https://doi.org/10.1016/j.it.2011.06.013
51. Vento-Tormo R., Efremova M., Botting R.A., Turco M.Y., Vento-Tormo M., Meyer K.B., Park J.-E., Stephenson E., Polański K., Goncalves A., Gardner L., Holmqvist S., Henriksson J., Zou A., Sharkey A.M., Millar B., Innes B., Wood L., Wilbrey-Clark A., Payne R.P., Ivarsson M.A., Lisgo S., Filby A., Rowitch D.H., Bulmer. J.N., Wright G.J., Stubbington M.J.T., Haniffa M., Moffett A., Teichmann S.A. Single-cell reconstruction of the early maternal–fetal interface in humans. Nature. 2018; 563 (7731): 347–53. DOI: https://doi.org/10.1038/s41586-018-0698-6.
52. Tokmadzic V.S., Tsuji Y., Bogovic T., Laskarin G., Cupurdija K., Strbo N., Koyama K., Okamura H., Podack E.R., Rukavina D. IL-18 is present at the maternal-fetal interface and enhances cytotoxic activity of decidual lymphocytes. Am. J. Reprod. Immunol. 2002; 48 (4): 191–200. DOI: https://doi.org/10.1034/j.1600-0897.2002.01132.x
53. Si L.F., Zhang S.Y., Gao C.S., Chen S.L., Zhao J., Cheng X.C. Effects of IFN-γ on IL-18 expression in pregnant rats and pregnancy outcomes. Asian-Australas J. Anim. Sci. 2013; 26 (10): 1399–405. DOI: https://doi.org/10.5713/ajas.2013.13101
54. Liu Z., Chen Y., Peng J.P. The effect on MHC class II expression and apoptosis in placenta by IFN-γ administration. Contraception. 2002; 65 (2): 177–84. DOI: https://doi.org/10.1016/s0010-7824(01)00277-3
55. Eriksson M., Meadows S.K., Basu S., Mselle T.F., Wira C.R., Sentman C.L. TLRs mediate IFN-gamma production by human uterine NK cells in endometrium. J. Immunol. 2006; 176 (10): 6219–24. DOI: https://doi.org/10.4049/jimmunol.176.10.6219
56. Croy B.A., He H., Esadeg S., Wei Q., McCartney D., Zhang J., Borzychowski A., Ashkar A.A., Black G.P., Evans S.S., Chantakru S., van den Heuvel M., Paffaro V.A. Jr, Yamada A.T. Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling. Reproduction. 2003; 126 (2): 149–60. DOI: https://doi.org/10.1530/rep.0.1260149
57. Rölle A., Pollmann J., Cerwenka A. Memory of infections: an emerging role for natural killer cells. PLoS Pathog. 2013; 9 (9): e1003548. DOI: https://doi.org/10.1371/journal.ppat.1003548
58. Berrien-Elliott M.M., Wagner J.A., Fehniger T.A. Human cytokine-induced memory-like natural killer cells. J. Innate Immun. 2015; 7 (6): 563–71. DOI: https://doi.org/10.1159/000382019
59. Goldman-Wohl D., Gamliel M., Mandelboim O., Yagel S. Learning from experience: cellular and molecular bases for improved outcome in subsequent pregnancies. Am. J. Obstet. Gynecol. 2019; 221 (3): 183–93. DOI: https://doi.org/10.1016/j.ajog.2019.02.037
60. Cerwenka A., Lanier L.L. Natural killer cell memory in infection, inflammation and cancer. Nat. Rev. Immunol. 2016; 16 (2): 112–23. DOI: https://doi.org/10.1038/nri.2015.9