{"paper_id":"ec03fc5e-e29f-43bb-acc0-a3c691c8a26c","body_text":"Abstract\nPurpose\nInvariant Natural Killer T cells (iNKT) are a specialized subset of T cells that use their T cell receptor to recognize self and foreign lipids presented by CD1d as cognate antigens. iNKT have been shown to have either protective or harmful roles in many pathological states, including microbial infection, autoimmune disease, allergic disease and cancer. Accumulating evidence seems to suggest that this unique T cell subset combines both classically innate and adaptive immunologic characteristic. Considering these recent data, the aim of work was to review the current knowledge about iNKT in eutopic and ectopic endometrium.\nMethods\nNarrative overview, synthesizing the findings of literature retrieved from searches of computerized databases.\nResults\nCurrently, the immune paradigm of reproduction is gradually changing shape: recent data confirmed that cytokine milieu influences the development and plasticity of different subtype of mononuclear cells, and in turn it can be influenced by the cytokine production of the latter. Among the different NKT cell populations, the recently characterized iNKT seems to share actions typical both of innate and adaptive immunity, being capable of secreting Th1 as well as Th2 cytokine pattern. Moreover, several subtypes of iNKT were identified, who partially express the same master transcription factors of the corresponding T cells counterpart.\nConclusions\nAlthough the data about iNKT’s actions in eutopic and ectopic endometrium are still scarce, it is possible to hypothesize that future investigation can shed light on this point, thus allowing a better knowledge about the regulation of these two microenvironments.\nSimilar content being viewed by others\nReferences\nIvanov S, Paget C, Trottein F (2014) Role of non-conventional T lymphocytes in respiratory infections: the case of the pneumococcus. PLoS Pathog 10:e1004300. doi:10.1371/journal.ppat.1004300\nBrigl M, Brenner MB (2004) CD1: antigen presentation and T cell function. Annu Rev Immunol 22:817–890. doi:10.1146/annurev.immunol.22.012703.104608\nBorg NA, Wun KS, Kjer-Nielsen L et al (2007) CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448:44–49. doi:10.1038/nature05907\nBrennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol 13:101–117. doi:10.1038/nri3369\nCohen NR, Brennan PJ, Shay T et al (2013) Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells. Nat Immunol 14:90–99. doi:10.1038/ni.2490\nTyznik AJ, Tupin E, Nagarajan NA et al (2008) Cutting edge: the mechanism of invariant NKT cell responses to viral danger signals. J Immunol 181:4452–4456\nSköld M, Stenström M, Sidobre S et al (2003) MHC-dependent and -independent modulation of endogenous Ly49 receptors on NK1.1+ T lymphocytes directed by T-cell receptor type. Immunology 110:313–321. doi:10.1046/j.1365-2567.2003.01741.x\nGodfrey DI, Rossjohn J (2011) New ways to turn on NKT cells. J Exp Med 208:1121–1125. doi:10.1084/jem.20110983\nMatsuda JL, Mallevaey T, Scott-Browne J, Gapin L (2008) CD1d-restricted iNKT cells, the “Swiss-Army knife” of the immune system. Curr Opin Immunol 20:358–368. doi:10.1016/j.coi.2008.03.018\nKawano T, Cui J, Koezuka Y et al (1997) CD1d-restricted and TCR-mediated activation of vα14 NKT cells by glycosylceramides. Science 278:1626–1629. doi:10.1126/science.278.5343.1626\nLee PT, Benlagha K, Teyton L, Bendelac A (2002) Distinct functional lineages of human V(α)24 natural killer T cells. J Exp Med 195:637–641. doi:10.1084/jem.20011908\nGumperz JE, Miyake S, Yamamura T, Brenner MB (2002) Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining. J Exp Med 195:625–636. doi:10.1084/jem.20011786\nBendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336. doi:10.1146/annurev.immunol.25.022106.141711\nKain L, Costanzo A, Webb B et al (2015) Endogenous ligands of natural killer T cells are alpha-linked glycosylceramides. Mol Immunol 68:94–97. doi:10.1016/j.molimm.2015.06.009\nWatarai H, Sekine-Kondo E, Shigeura T et al (2012) Development and function of invariant natural killer T cells producing T(h)2- and T(h)17-cytokines. PLoS Biol 10:e1001255. doi:10.1371/journal.pbio.1001255\nYu ED, Girardi E, Wang J, Zajonc DM (2011) Cutting edge: structural basis for the recognition of β-linked glycolipid antigens by invariant NKT cells. J Immunol 187:2079–2083. doi:10.4049/jimmunol.1101636\nBai L, Constantinides MG, Thomas SY et al (2012) Distinct APCs explain the cytokine bias of α-galactosylceramide variants in vivo. J Immunol 188:3053–3061. doi:10.4049/jimmunol.1102414\nTaniguchi M, Tashiro T, Dashtsoodol N et al (2009) The specialized iNKT cell system recognizes glycolipid antigens and bridges the innate and acquired immune systems with potential applications for cancer therapy. Int Immunol 22:1–6. doi:10.1093/intimm/dxp104\nBrigl M, Bry L, Kent SC et al (2003) Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 4:1230–1237. doi:10.1038/ni1002\nVan Kaer L, Parekh VV, Wu L (2011) Invariant natural killer T cells: bridging innate and adaptive immunity. Cell Tissue Res 343:43–55. doi:10.1007/s00441-010-1023-3\nNagarajan NA, Kronenberg M (2007) Invariant NKT cells amplify the innate immune response to lipopolysaccharide. J Immunol 178:2706–2713. doi:10.4049/jimmunol.178.5.2706\nSalio M, Speak AO, Shepherd D et al (2007) Modulation of human natural killer T cell ligands on TLR-mediated antigen-presenting cell activation. Proc Natl Acad Sci USA 104:20490–20495. doi:10.1073/pnas.0710145104\nTupin E, Kinjo Y, Kronenberg M (2007) The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 5:405–417. doi:10.1038/nrmicro1657\nKinjo Y, Kitano N, Kronenberg M (2013) The role of invariant natural killer T cells in microbial immunity. J Infect Chemother 19:560–570. doi:10.1007/s10156-013-0638-1\nKim EY, Battaile JT, Patel AC et al (2008) Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med 14:633–640. doi:10.1038/nm1770\nVan Kaer L, Parekh VV, Wu L (2013) Invariant natural killer T cells as sensors and managers of inflammation. Trends Immunol 34:50–58. doi:10.1016/j.it.2012.08.009\nScott-Browne JP, Matsuda JL, Mallevaey T et al (2007) Germline-encoded recognition of diverse glycolipids by natural killer T cells. Nat Immunol 8:1105–1113. doi:10.1038/ni1510\nArrenberg P, Halder R, Dai Y et al (2010) Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a beta-linked self-glycolipid. Proc Natl Acad Sci USA 107:10984–10989. doi:10.1073/pnas.1000576107\nRossjohn J, Pellicci DG, Patel O et al (2012) Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev Immunol 12:845–857. doi:10.1038/nri3328\nRhost S, Löfbom L, Rynmark BM et al (2012) Identification of novel glycolipid ligands activating a sulfatide-reactive, CD1d-restricted, type II natural killer T lymphocyte. Eur J Immunol 42:2851–2860. doi:10.1002/eji.201142350\nBerzofsky JA, Terabe M (2009) The contrasting roles of NKT cells in tumor immunity. Curr Mol Med 9:667–672\nThomas SY, Hou R, Boyson JE et al (2003) CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. J Immunol 171:2571–2580. doi:10.4049/jimmunol.171.5.2571\nDoisne J-M, Becourt C, Amniai L et al (2009) Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor γt+ and respond preferentially under inflammatory conditions. J Immunol 183:2142–2149. doi:10.4049/jimmunol.0901059\nScanlon ST, Thomas SY, Ferreira CM et al (2011) Airborne lipid antigens mobilize resident intravascular NKT cells to induce allergic airway inflammation. J Exp Med 208:2113–2124. doi:10.1084/jem.20110522\nBerzins SP, Smyth MJ, Baxter AG (2011) Presumed guilty: natural killer T cell defects and human disease. Nat Rev Immunol 11:131–142. doi:10.1038/nri2904\nThomas SY, Scanlon ST, Griewank KG et al (2011) PLZF induces an intravascular surveillance program mediated by long-lived LFA-1-ICAM-1 interactions. J Exp Med 208:1179–1188. doi:10.1084/jem.20102630\nField JJ, Nathan DG, Linden J (2011) Targeting iNKT cells for the treatment of sickle cell disease. Clin Immunol 140:177–183. doi:10.1016/j.clim.2011.03.002\nHansen CHF, Nielsen DS, Kverka M et al (2012) Patterns of early gut colonization shape future immune responses of the host. PLoS One. doi:10.1371/journal.pone.0034043\nChang YJ, Kim HY, Albacker LA et al (2011) Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J Clin Invest 121:57–69. doi:10.1172/JCI44845\nYuan J, Nguyen CK, Liu X et al (2012) Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis. Science 335:1195–1200. doi:10.1126/science.1216557\nDarmoise A, Teneberg S, Bouzonville L et al (2010) Lysosomal α-galactosidase controls the generation of self lipid antigens for natural killer T cells. Immunity 33:216–228. doi:10.1016/j.immuni.2010.08.003\nRachitskaya AV, Hansen AM, Horai R et al (2008) Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J Immunol 180:5167–5171. doi:10.4049/jimmunol.180.8.5167\nSchipper HS, Rakhshandehroo M, van de Graaf SFJ et al (2012) Natural killer T cells in adipose tissue prevent insulin resistance. J Clin Invest 122:3343–3354. doi:10.1172/JCI62739\nLynch L, Nowak M, Varghese B et al (2012) Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37:574–587. doi:10.1016/j.immuni.2012.06.016\nBosma A, Abdel-Gadir A, Isenberg DA et al (2012) Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36:477–490. doi:10.1016/j.immuni.2012.02.008\nKing IL, Fortier A, Tighe M et al (2011) Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. Nat Immunol 13:44–50. doi:10.1038/ni.2172\nMonteiro M, Almeida CF, Caridade M et al (2010) Identification of regulatory Foxp3+ invariant NKT cells induced by TGF-beta. J Immunol 185:2157–2163. doi:10.4049/jimmunol.1000359\nBezbradica JS, Stanic AK, Matsuki N et al (2005) Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J Immunol 174:4696–4705. doi:10.4049/jimmunol.174.8.4696\nFujii S-I, Liu K, Smith C et al (2004) The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation. J Exp Med 199:1607–1618. doi:10.1084/jem.20040317\nBrigl M, Tatituri RVV, Watts GFM et al (2011) Innate and cytokine-driven signals, rather than microbial antigens, dominate in natural killer T cell activation during microbial infection. J Exp Med 208:1163–1177. doi:10.1084/jem.20102555\nSchmieg J, Yang G, Franck RW et al (2005) Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion. Proc Natl Acad Sci USA 102:1127–1132. doi:10.1073/pnas.0408288102\nSada-Ovalle I, Chiba A, Gonzales A et al (2008) Innate invariant NKT cells recognize Mycobacterium tuberculosis-infected macrophages, produce interferon-gamma, and kill intracellular bacteria. PLoS Pathog 4:e1000239. doi:10.1371/journal.ppat.1000239\nNieuwenhuis EES, Matsumoto T, Exley M et al (2002) CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung. Nat Med 8:588–593. doi:10.1038/nm0602-588\nMetelitsa LS (2011) Anti-tumor potential of type-I NKT cells against CD1d-positive and CD1d-negative tumors in humans. Clin Immunol 140:119–129. doi:10.1016/j.clim.2010.10.005\nVomhof-DeKrey EE, Yates J, Leadbetter EA (2014) Invariant NKT cells provide innate and adaptive help for B cells. Curr Opin Immunol 28:12–17. doi:10.1016/j.coi.2014.01.007\nVomhof-DeKrey EE, Yates J, Hägglöf T et al (2015) Cognate interaction with iNKT cells expands IL-10-producing B regulatory cells. Proc Natl Acad Sci USA 112:12474–12479. doi:10.1073/pnas.1504790112\nDellabona P, Abrignani S, Casorati G (2014) iNKT cell help to B cells: a cooperative job between innate and adaptive immune responses. Eur J Immunol. doi:10.1002/eji.201344399.This\nLappas CM, Day Y-J, Marshall MA et al (2006) Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation. J Exp Med 203:2639–2648. doi:10.1084/jem.20061097\nKawakami K, Yamamoto N, Kinjo Y et al (2003) Critical role of Vα14+ natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection. Eur J Immunol 33:3322–3330. doi:10.1002/eji.200324254\nDe Santo C, Arscott R, Booth S et al (2010) Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat Immunol 11:1039–1046. doi:10.1038/ni.1942\nGuerin LR, Prins JR, Robertson SA (2009) Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum Reprod Update 15:517–535. doi:10.1093/humupd/dmp004\nMunoz-Suano A, Hamilton AB, Betz AG (2011) Gimme shelter: the immune system during pregnancy. Immunol Rev 241:20–38. doi:10.1111/j.1600-065X.2011.01002.x\nFaulk WP, Temple A (1976) Distribution of β2 microglobulin and HLA in chorionic villi of human placentae. Nature 262:799–802. doi:10.1038/260170a0\nKing A, Boocock C, Sharkey AM et al (1996) Evidence for the expression of HLAA-C class I mRNA and protein by human first trimester trophoblast. J Immunol 156:2068–2076. doi:10.1016/0165-0378(96)87783-7\nKovats S, Main EK, Librach C et al (1990) A class I antigen, HLA-G, expressed in human trophoblasts. Science 248:220–223. doi:10.1126/science.2326636\nRaghupathy R, Makhseed M, Azizieh F et al (1999) Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions. Cell Immunol 196:122–130. doi:10.1006/cimm.1999.1532\nVince GS, Johnson PM (2000) Leucocyte populations and cytokine regulation in human uteroplacental tissues. Biochem Soc Trans 28:191–195\nRaghupathy R (1997) Th1-type immunity is incompatible with successful pregnancy. Immunol Today 18:478–482. doi:10.1016/S0167-5699(97)01127-4\nWegmann TG, Lin H, Guilbert L, Mosmann TR (1993) Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 14:353–356. doi:10.1016/0167-5699(93)90235-D\nSaito S, Shima T, Inada K, Nakashima A (2013) Which types of regulatory T cells play important roles in implantation and pregnancy maintenance? Am J Reprod Immunol 69:340–345. doi:10.1111/aji.12101\nSomerset DA, Zheng Y, Kilby MD et al (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25 + CD4 + regulatory T-cell subset. Immunology 112:38–43. doi:10.1111/j.1365-2567.2004.01869.x\nPot C, Apetoh L, Kuchroo VK (2011) Type 1 regulatory T cells (Tr1) in autoimmunity. Semin Immunol 23:202–208. doi:10.1016/j.biotechadv.2011.08.021.Secreted\nRoncarolo MG, Gregori S, Bacchetta R, Battaglia M (2014) Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications. Curr Top Microbiol Immunol 380:39–68. doi:10.1007/978-3-662-43492-5_3\nGregori S, Tomasoni D, Pacciani V et al (2010) Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood 116:935–944. doi:10.1182/blood-2009-07-234872\nArruvito L, Sotelo AI, Billordo A, Fainboim L (2010) A physiological role for inducible FOXP3(+) Treg cells. Lessons from women with reproductive failure. Clin Immunol 136:432–441. doi:10.1016/j.clim.2010.05.002\nJiang SP, Vacchio MS (1998) Multiple mechanisms of peripheral T cell tolerance to the fetal “allograft”. J Immunol 160:3086–3090\nTafuri A, Alferink J, Möller P et al (1995) T cell awareness of paternal alloantigens during pregnancy. Science 270:630–633. doi:10.1126/science.270.5236.630\nHunt JS, Vassmer D, Ferguson TA, Miller L (1997) Fas ligand is positioned in mouse uterus and placenta to prevent trafficking of activated leukocytes between the mother and the conceptus. J Immunol (Baltimore, Md 1950) 158:4122–4128\nKing A, Burrows T, Verma S et al (1998) Human uterine lymphocytes. Hum Reprod Update 4:480–485. doi:10.1093/humupd/4.5.480\nMincheva-Nilsson L, Hammarström S, Hammarström ML (1992) Human decidual leukocytes from early pregnancy contain high numbers of gamma delta + cells and show selective down-regulation of alloreactivity. J Immunol 149:2203–2211\nBulmer JN, Williams PJ, Lash GE (2010) Immune cells in the placental bed. Int J Dev Biol 54:281–294. doi:10.1387/ijdb.082763jb\nUemura Y, Suzuki M, Liu T-Y et al (2008) Role of human non-invariant NKT lymphocytes in the maintenance of type 2 T helper environment during pregnancy. Int Immunol 20:405–412. doi:10.1093/intimm/dxn001\nBoyson JE, Rybalov B, Koopman LA et al (2002) CD1d and invariant NKT cells at the human maternal-fetal interface. Proc Natl Acad Sci USA 99:13741–13746. doi:10.1073/pnas.162491699\nDang Y, Heyborne KD (2001) Cutting edge: regulation of uterine NKT cells by a fetal class I molecule other than CD1. J Immunol 166:3641–3644\nHuang Y, Zhu XY, Du MR, Li DJ (2008) Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy. J Immunol (Baltimore, Md 1950) 180:2367–2375. doi:10.4049/jimmunol.180.4.2367\nIto K, Karasawa M, Kawano T et al (2000) Involvement of decidual Vα14 NKT cells in abortion. Proc Natl Acad Sci USA 97:740–744\nJakovac H, Grebic D, Grubic-Kezele T et al (2013) Endoplasmic reticulum resident heat shock protein-gp96 as morphogenetic and immunoregulatory factor in syngeneic pregnancy. Histol Histopathol 28:1285–1298\nHurtado CW, Golden-mason L, Brocato M et al (2010) Innate immune function in placenta and cord blood of hepatitis C-seropositive mother-infant dyads. PLoS ONE 5:e12232. doi:10.1371/journal.pone.0012232\nKrízan J, Cuchalová L, Síma P et al (2009) Altered distribution of NK and NKT cells in follicular fluid is associated with IVF outcome. J Reprod Immunol 82:84–88. doi:10.1016/j.jri.2009.05.005\nFukui A, Fujii S, Yamaguchi E et al (1999) Natural killer cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilization. Am J Reprod Immunol 41:413–422\nCoulam CB, Roussev RG (2003) Increasing circulating T-cell activation markers are linked to subsequent implantation failure after transfer of in vitro fertilized embryos. Am J Reprod Immunol 50:340–345\nDosiou C, Giudice LC (2005) Natural killer cells in pregnancy and recurrent pregnancy loss: endocrine and immunologic perspectives. Endocr Rev 26:44–62. doi:10.1210/er.2003-0021\nMaeda N, Izumiya C, Yamamoto Y et al (2002) Increased killer inhibitory receptor KIR2DL1 expression among natural killer cells in women with pelvic endometriosis. Fertil Steril 77:297–302\nYang JH, Chen MJ, Chen HF et al (2004) Decreased expression of killer cell inhibitory receptors on natural killer cells in eutopic endometrium in women with adenomyosis. Hum Reprod 19:1974–1978. doi:10.1093/humrep/deh372\nYang OO, Racke FK, Nguyen PT et al (2000) CD1d on myeloid dendritic cells stimulates cytokine secretion from and cytolytic activity of Vα24JαQ T cells: a feedback mechanism for immune regulation. J Immunol 165:3756–3762. doi:10.4049/jimmunol.165.7.3756\nArruvito L, Sanz M, Banham AH, Fainboim L (2007) Expansion of CD4+ CD25+ and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol 178:2572–2578. doi:10.4049/jimmunol.178.4.2572\nPeralta CG, Han VK, Horrocks J et al (2008) CD56bright cells increase expression of α4 integrin at ovulation in fertile cycles. J Leukoc Biol 84:1065–1074. doi:10.1189/jlb.0308164\nShimada S, Nishida R, Takeda M et al (2006) Natural killer, natural killer T, helper and cytotoxic T cells in the decidua from sporadic miscarriage. Am J Reprod Immunol 56:193–200. doi:10.1111/j.1600-0897.2006.00417.x\nShimada S, Kato EH, Morikawa M et al (2004) No difference in natural killer or natural killer T-cell population, but aberrant T-helper cell population in the endometrium of women with repeated miscarriage. Hum Reprod 19:1018–1024. doi:10.1093/humrep/deh159\nSzereday L, Miko E, Meggyes M et al (2012) Commitment of decidual haematopoietic progenitor cells in first trimester pregnancy. Am J Reprod Immunol 67:9–16. doi:10.1111/j.1600-0897.2011.01029.x\nLi LP, Fang YC, Dong GF et al (2012) Depletion of invariant NKT cells reduces inflammation-induced preterm delivery in mice. J Immunol 188:4681–4689. doi:10.4049/jimmunol.1102628\nLing B, Yao F, Zhou Y et al (2007) Cell-mediated immunity imbalance in patients with intrahepatic cholestasis of pregnancy. Cell Mol Immunol 4:71–75\nMarkel G, Wolf D, Hanna J et al (2002) Pivotal role of CEACAM1 protein in the inhibition of activated decidual lymphocyte functions. J Clin Invest 110:943–953. doi:10.1172/JCI200215643\nGiudice LC, Kao LC (2004) Endometriosis. Lancet 364:1789–1799. doi:10.1016/S0140-6736(04)17403-5\nTriolo O, Laganà AS, Sturlese E (2013) Chronic pelvic pain in endometriosis: an overview. J Clin Med Res 5:153–163\nLaganà AS, Condemi I, Retto G et al (2015) Analysis of psychopathological comorbidity behind the common symptoms and signs of endometriosis. Eur J Obstet Gynecol Reprod Biol 194:30–33. doi:10.1016/j.ejogrb.2015.08.015\nGreco E, Pellicano M, Di Spiezio Sardo A et al (2004) Etiopathogenesis of endometriosis related infertility. Minerva Ginecol 56:259–270\nPellicano M, Bramante S, Guida M et al (2008) Ovarian endometrioma: postoperative adhesions following bipolar coagulation and suture. Fertil Steril 89:796–799. doi:10.1016/j.fertnstert.2006.11.201\nLaganà AS, Sturlese E, Retto G et al (2013) Interplay between misplaced müllerian-derived stem cells and peritoneal immune dysregulation in the pathogenesis of endometriosis. Obstet Gynecol Int 2013:527041. doi:10.1155/2013/527041\nSalmeri FM, Lagana AS, Sofo V et al (2015) Behavior of tumor necrosis factor- and tumor necrosis factor receptor 1/tumor necrosis factor receptor 2 system in mononuclear cells recovered from peritoneal fluid of women with endometriosis at different stages. Reprod Sci 22:165–172. doi:10.1177/1933719114536472\nSturlese E, Salmeri FM, Retto G et al (2011) Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. J Reprod Immunol 92:74–81\nSofo V, Götte M, Laganà AS et al (2015) Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease. Arch Gynecol Obstet. doi:10.1007/s00404-015-3739-5\nProvinciali M, Di Stefano G, Muzzioli M et al (1995) Relationship between 17-beta-estradiol and prolactin in the regulation of natural killer cell activity during progression of endometriosis. J Endocrinol Invest 18:645–652\nGarzetti GG, Ciavattini A, Provinciali M et al (1993) Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity. Obs Gynecol 81:665–668\nPolanczyk MJ, Hopke C, Huan J et al (2005) Enhanced FoxP3 expression and Treg cell function in pregnant and estrogen-treated mice. J Neuroimmunol 170:85–92. doi:10.1016/j.jneuroim.2005.08.023\nPolanczyk MJ, Hopke C, Vandenbark AA, Offner H (2007) Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1). Int Immunol 19:337–343. doi:10.1093/intimm/dxl151\nGuo S, Zhang Y, Wang L, Qiu W (2012) Association of natural killer T cells with staging of endometriosis. Nan Fang Yi Ke Da Xue Xue Bao 32:1322–1324\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nConflict of interest\nThe authors have no proprietary, financial, professional or other personal interest of any nature in any product, service or company. The authors alone are responsible for the content and writing of the paper.\nRights and permissions\nAbout this article\nCite this article\nLaganà, A.S., Triolo, O., Salmeri, F.M. et al. Natural Killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner. Arch Gynecol Obstet 293, 941–949 (2016). https://doi.org/10.1007/s00404-015-4004-7\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-015-4004-7","source_license":"public-domain-us","license_restricted":false}