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From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for other, bacterial antigens to be described. Given the paucity of known bacterial iNKT cell antigens, it appeared as if iNKT cells play a very specialist role in the protection against few, rare and unusual pathogenic bacteria. However, in the last few years several publications painted a very different picture, suggesting that antigens for iNKT cells are found almost ubiquitous in the environment. These environmental iNKT cell antigens can shape the distribution, phenotype and function of iNKT cells. Here, these recent findings will be reviewed and their implications for the field will be outlined.

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Abbreviations

αGalCer:

α-Galactosylceramide

EoE:

Eosinophilic esophagitis

HDE:

House dust extract

MHC:

Major histocompatibility complex

TCR:

T cell receptor

Th:

T helper type

Vα14i :

Invariant Vα14–Jα18 TCR rearrangement

Vα24i :

Invariant Vα24–Jα18 TCR rearrangement

References

  • Agea E, Russano A, Bistoni O et al (2005) Human CD1-restricted T cell recognition of lipids from pollens. J Exp Med 202:295–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albacker LA, Chaudhary V, Chang Y-J et al (2013) Invariant natural killer T cells recognize a fungal glycosphingolipid that can induce airway hyperreactivity. Nat Med 19:1297–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amprey JL, Im JS, Turco SJ et al (2004) A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan. J Exp Med 200:895–904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • An D, Oh SF, Olszak T et al (2014) Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer t cells. Cell 156:123–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336

    Article  CAS  PubMed  Google Scholar 

  • Ben-Menachem G, Kubler-Kielb J, Coxon B et al (2003) A newly discovered cholesteryl galactoside from Borrelia burgdorferi. Proc Natl Acad Sci USA 100:7913–7918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berzins SP, Ritchie DS (2014) Natural killer T cells: drivers or passengers in preventing human disease? Nat Rev Immunol 14:640–646

    Article  CAS  PubMed  Google Scholar 

  • Brennan PJ, Brigl M, Brenner MB (2013) Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev 13:101–117

    CAS  Google Scholar 

  • Brennan PJ, Tatituri RVV, Heiss C et al (2014) Activation of iNKT cells by a distinct constituent of the endogenous glucosylceramide fraction. Proc Natl Acad Sci USA 111:13433–13438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brossay L, Kronenberg M (1999) Highly conserved antigen-presenting function of CD1d molecules. Immunogenetics 50:146–151

    Article  CAS  PubMed  Google Scholar 

  • Brossay L, Chioda M, Burdin N et al (1998) CD1d-mediated recognition of an alpha-galactosylceramide by natural killer T cells is highly conserved through mammalian evolution. J Exp Med 188:1521–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chan AC, Leeansyah E, Cochrane A et al (2013) Ex-vivo analysis of human natural killer T cells demonstrates heterogeneity between tissues and within established CD4(+) and CD4(−) subsets. Clin Exp Immunol 172:129–137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang P-P, Barral P, Fitch J et al (2011a) Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses. Nat Immunol 13:35–43

    Article  PubMed  Google Scholar 

  • Chang Y-J, Kim HY, Albacker LA et al (2011b) Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity. J Clin Invest 121:57–69

    Article  CAS  PubMed  Google Scholar 

  • D’Andrea A, Goux D, De Lalla C et al (2000) Neonatal invariant Valpha24 + NKT lymphocytes are activated memory cells. Eur J Immunol 30:1544–1550

    Article  PubMed  Google Scholar 

  • de Lalla C, Festuccia N, Albrecht I et al (2008) Innate-like effector differentiation of human invariant NKT cells driven by IL-7. J Immunol 180:4415–4424

    Article  PubMed  Google Scholar 

  • DeKruyff RH, Yu S, Kim HY et al (2014) Innate immunity in the lung regulates the development of asthma. Immunol Rev 260:235–248

    Article  CAS  PubMed  Google Scholar 

  • Dumler JS (2005) Anaplasma and Ehrlichia infection. Ann N Y Acad Sci 1063:361–373

    Article  PubMed  Google Scholar 

  • Dutt P, Shukla JS, Ventateshaiah SU et al (2015) Allergen-induced interleukin-18 promotes experimental eosinophilic oesophagitis in mice. Immunol Cell Biol 93:849–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eger KA, Sundrud MS, Motsinger AA et al (2006) Human natural killer T cells are heterogeneous in their capacity to reprogram their effector functions. PLoS One 1:e50

    Article  PubMed  PubMed Central  Google Scholar 

  • Engel I, Kronenberg M (2012) Making memory at birth: understanding the differentiation of natural killer T cells. Curr Opin Immunol 24:184–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Exley MA, Hou R, Shaulov A et al (2008) Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR α-chain CDR3 loop. Eur J Immunol 38:1756–1766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fujii S, Shimizu K, Okamoto Y et al (2013) NKT cells as an ideal anti-tumor immunotherapeutic. Front Immunol 4:409

    Article  PubMed  PubMed Central  Google Scholar 

  • Girardi E, Yu ED, Li Y et al (2011) Unique interplay between sugar and lipid in determining the antigenic potency of bacterial antigens for NKT cells. PLoS Biol 9:e1001189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Godfrey DI, Pellicci DG, Rossjohn J (2013) NKT cells: the smoking gun in fungal-induced asthma? Nat Med 19:1210–1211

    Article  CAS  PubMed  Google Scholar 

  • Hagihara M, Gansuvd B, Ueda Y et al (2002) Killing activity of human umbilical cord blood-derived TCRValpha24(+) NKT cells against normal and malignant hematological cells in vitro: a comparative study with NK cells or OKT3 activated T lymphocytes or with adult peripheral blood NKT cells. Cancer Immunol Immunother 51:1–8

    Article  CAS  PubMed  Google Scholar 

  • Harner S, Noessner E, Nadas K et al (2011) Cord blood Valpha24-vbeta11 natural killer T cells display a Th2-chemokine receptor profile and cytokine responses. PLoS One 6:e15714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heller F, Fuss IJ, Nieuwenhuis EE et al (2002) Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17:629–638

    Article  CAS  PubMed  Google Scholar 

  • Hirai Y, Haque M, Yoshida T et al (1995) Unique cholesteryl glucosides in Helicobacter pylori: composition and structural analysis. J Bacteriol 177:5327–5333

    CAS  PubMed  PubMed Central  Google Scholar 

  • Horner AA (2010) Regulation of aeroallergen immunity by the innate immune system: laboratory evidence for a new paradigm. J Innate Immun 2:107–113

    Article  CAS  PubMed  Google Scholar 

  • Hsueh PR, Teng LJ, Yang PC et al (1998) Nosocomial infections caused by Sphingomonas paucimobilis: clinical features and microbiological characteristics. Clin Infect Dis 26:676–681

    Article  CAS  PubMed  Google Scholar 

  • Huang YJ, Nelson CE, Brodie EL et al (2011) Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J Allergy Clin Immunol 127(372–381):e1–e3

    Google Scholar 

  • Ito Y, Vela JL, Matsumura F et al (2013) Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells. PLoS One 8:e78191

    Article  PubMed  PubMed Central  Google Scholar 

  • Ivanov II, Atarashi K, Manel N et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139:485–498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang J, Karimi O, Ouburg S et al (2012) Interruption of CXCL13-CXCR5 axis increases upper genital tract pathology and activation of NKT cells following Chlamydial genital infection. PLoS One 7:e47487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jyonouchi S, Abraham V, Orange JS et al (2011) Invariant natural killer T cells from children with versus without food allergy exhibit differential responsiveness to milk-derived sphingomyelin. J Allergy Clin Immunol 128(102–109):e13

    PubMed  Google Scholar 

  • Jyonouchi S, Smith CL, Saretta F et al (2014) Invariant natural killer T cells in children with eosinophilic esophagitis. Clin Exp Allergy 44:58–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kain L, Webb B, Anderson BL et al (2014) The Identification of the endogenous ligands of natural killer t cells reveals the presence of mammalian a-linked glycosylceramides. Immunity 41:543–554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karmakar S, Paul J, De T (2011) Leishmania donovani glycosphingolipid facilitates antigen presentation by inducing relocation of CD1d into lipid rafts in infected macrophages. Eur J Immunol 41:1376–1387

    Article  CAS  PubMed  Google Scholar 

  • Kawakami K, Yamamoto N, Kinjo Y et al (2003) Critical role of Valpha14 + natural killer T cells in the innate phase of host protection against Streptococcus pneumoniae infection. Eur J Immunol 33:3322–3330

    Article  CAS  PubMed  Google Scholar 

  • Kawano T, Cui J, Koezuka Y et al (1997) CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278:1626–1629

    Article  CAS  PubMed  Google Scholar 

  • Kenyon CR, Osbak K (2014) Recent progress in understanding the epidemiology of bacterial vaginosis. Curr Opin Obstet Gynecol 26:448–454

    Article  PubMed  Google Scholar 

  • King 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

    Article  PubMed  Google Scholar 

  • Kinjo Y, Kronenberg M (2009) Detection of microbes by natural killer T cells. In: Schoenberger et al (eds) Crossroads between innate and adaptive immunity II. Springer, New York, pp 17–26

  • Kinjo Y, Wu D, Kim G et al (2005) Recognition of bacterial glycosphingolipids by natural killer T cells. Nature 434:520–525

    Article  CAS  PubMed  Google Scholar 

  • Kinjo Y, Tupin E, Wu D et al (2006) Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria. Nat Immunol 7:978–986

    Article  CAS  PubMed  Google Scholar 

  • Kinjo Y, Illarionov P, Vela JL et al (2011) Invariant natural killer T cells recognize glycolipids from pathogenic Gram-positive bacteria. Nat Immunol 12:966–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kronenberg M (2005) Towards an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 23:877–900

    Article  CAS  PubMed  Google Scholar 

  • Laskin AI, White DC (1999) Preface to special issue on Sphingomonas. J Ind Microbiol Biotechnol 23:231

    Article  CAS  PubMed  Google Scholar 

  • Lexmond WS, Neves JF, Nurko S et al (2014) Involvement of the iNKT cell pathway is associated with early-onset eosinophilic esophagitis and response to allergen avoidance therapy. Am J Gastroenterol 109:646–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang S, Webb T, Li Z (2014) Probiotic antigens stimulate hepatic natural killer T cells. Immunology 141:203–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin D, Koskella B (2015) Friend and foe: factors influencing the movement of the bacterium Helicobacter pylori along the parasitism-mutualism continuum. Evol Appl 8:9–22

    Article  PubMed  Google Scholar 

  • Loh L, Ivarsson MA, Michaelsson J et al (2014) Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine. Mucosal Immunol 7:1233–1243

    Article  CAS  PubMed  Google Scholar 

  • Lotter H, Gonzalez-Roldan N, Lindner B et al (2009) Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathog 5:e1000434

    Article  PubMed  PubMed Central  Google Scholar 

  • Lynch L, Michelet X, Zhang S et al (2015) Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue. Nat Immunol 16:85–95

    Article  CAS  PubMed  Google Scholar 

  • Matsuda JL, Gapin L, Baron JL et al (2003) Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci USA 100:8395–8400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mattner J, Debord KL, Ismail N et al (2005) Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections. Nature 434:525–529

    Article  CAS  PubMed  Google Scholar 

  • Mattner J, Savage PB, Leung P et al (2008) Liver autoimmunity triggered by microbial activation of natural killer T cells. Cell Host Microbe 3:304–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazmanian SK, Kasper DL (2006) The love–hate relationship between bacterial polysaccharides and the host immune system. Nat Rev Immunol 6:849–858

    Article  CAS  PubMed  Google Scholar 

  • Mirotti L, Florsheim E, Rundqvist L et al (2013) Lipids are required for the development of Brazil nut allergy: the role of mouse and human iNKT cells. Allergy 68:74–83

    Article  CAS  PubMed  Google Scholar 

  • Montoya CJ, Pollard D, Martinson J et al (2007) Characterization of human invariant natural killer T subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6B11. Immunology 122:1–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morita M, Motoki K, Akimoto K et al (1995) Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice. J Med Chem 38:2176–2187

    Article  CAS  PubMed  Google Scholar 

  • Mshvildadze M, Neu J, Shuster J et al (2010) Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr 156:20–25

    Article  PubMed  PubMed Central  Google Scholar 

  • Neef A, Witzenberger R, Kampfer P (1999) Detection of sphingomonads and in situ identification in activated sludge using 16S rRNA-targeted oligonucleotide probes. J Ind Microbiol Biotechnol 23:261–267

    Article  CAS  PubMed  Google Scholar 

  • Nieuwenhuis EE, Matsumoto T, Lindenbergh D et al (2009) Cd1d-dependent regulation of bacterial colonization in the intestine of mice. J Clin Invest 119:1241–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Konek JJ, Berzofsky JA, Terabe M (2012) Immune regulation of tumor immunity by NKT cells. In: Terabe M, Berzofsky JA (eds) Natural killer T cells. Springer, New York, pp 55–70

    Chapter  Google Scholar 

  • Olafsson S, Gudjonsson H, Selmi C et al (2004) Antimitochondrial antibodies and reactivity to N. aromaticivorans proteins in icelandic patients with primary biliary cirrhosis and their relatives. Am J Gastroenterol 99:2143–2146

    Article  CAS  PubMed  Google Scholar 

  • Olson CMJ, Bates TC, Izadi H et al (2009) Local production of IFN-gamma by invariant NKT cells modulates acute Lyme carditis. J Immunol 182:3728–3734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olszak T, An D, Zeissig S et al (2012) Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336:489–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng Y, Zhao L, Shekhar S et al (2012) The glycolipid exoantigen derived from Chlamydia muridarum activates invariant natural killer T cells. Cell Mol Immunol 9:361–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perola O, Nousiainen T, Suomalainen S et al (2002) Recurrent Sphingomonas paucimobilis -bacteraemia associated with a multi-bacterial water-borne epidemic among neutropenic patients. J Hosp Infect 50:196–201

    Article  CAS  PubMed  Google Scholar 

  • Rajavelu P, Rayapudi M, Moffitt M et al (2012) Significance of para-esophageal lymph nodes in food or aeroallergen-induced iNKT cell-mediated experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 302:G645–G654

    Article  CAS  PubMed  Google Scholar 

  • Rautava S, Collado MC, Salminen S et al (2012) Probiotics modulate host-microbe interaction in the placenta and fetal gut: a randomized, double-blind, placebo-controlled trial. Neonatology 102:178–184

    Article  PubMed  Google Scholar 

  • Rayapudi M, Rajavelu P, Zhu X et al (2014) Invariant natural killer T-cell neutralization is a possible novel therapy for human eosinophilic esophagitis. Clin Transl Immunol 3:e9

    Article  CAS  Google Scholar 

  • Rossjohn J, Pellicci DG, Patel O et al (2012) Recognition of CD1d-restricted antigens by natural killer T cells. Nat Rev 12:845–857

    CAS  Google Scholar 

  • Sag D, Krause P, Hedrick CC et al (2014) IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset. J Clin Invest 124:3725–3740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salio M, Silk JD, Yvonne Jones E et al (2014) Biology of CD1- and MR1-restricted T cells. Annu Rev Immunol 32:323–366

    Article  CAS  PubMed  Google Scholar 

  • Satokari R, Grönroos T, Laitinen K et al (2009) Bifidobacteriumand lactobacillusDNA in the human placenta. Lett Appl Microbiol 48:8–12

    Article  CAS  PubMed  Google Scholar 

  • Selmi C, Balkwill DL, Invernizzi P et al (2003) Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium. Hepatology 38:1250–1257

    Article  CAS  PubMed  Google Scholar 

  • Simoni Y, Diana J, Ghazarian L et al (2013) Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: are we close to reality? Clin Exp Immunol 171:8–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh AK, Gaur P, Das SN (2014) Natural killer T cell anergy, co-stimulatory molecules and immunotherapeutic interventions. Hum Immunol 75:250–260

    Article  CAS  PubMed  Google Scholar 

  • Sriram V, Du W, Gervay-Hague J et al (2005) Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells. Eur J Immunol 35:1692–1701

    Article  CAS  PubMed  Google Scholar 

  • Stetson DB, Mohrs M, Reinhardt RL et al (2003) Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med 198:1069–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tonti E, Fedeli M, Napolitano A et al (2012) Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4+ T cell help. J Immunol 188:3217–3222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tupin E, Benhnia MR, Kinjo Y et al (2008) NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi. Proc Natl Acad Sci USA 105:19863–19868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueda Y, Hagihara M, Gansuvd B et al (2003) The effects of alphaGalCer-induced TCRValpha24 Vbeta11(+) natural killer T cells on NK cell cytotoxicity in umbilical cord blood. Cancer Immunol Immunother 52:625–631

    Article  CAS  PubMed  Google Scholar 

  • van der Vliet HJ, Nishi N, de Gruijl TD et al (2000) Human natural killer T cells acquire a memory-activated phenotype before birth. Blood 95:2440–2442

    Google Scholar 

  • Wechsler JB, Bryce PJ (2014) Allergic mechanisms in eosinophilic esophagitis. Gastroenterol Clin North Am 43:281–296

    Article  PubMed  PubMed Central  Google Scholar 

  • Wei B, Wingender G, Fujiwara D et al (2010) Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells. J Immunol 184:1218–1226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White DC, Sutton SD, Ringelberg DB (1996) The genus Sphingomonas: physiology and ecology. Curr Opin Biotechnol 7:301–306

    Article  CAS  PubMed  Google Scholar 

  • Wieland Brown LC, Penaranda C, Kashyap PC et al (2013) Production of α-galactosylceramide by a prominent member of the human gut microbiota. PLoS Biol 11:e1001610

    Article  PubMed  PubMed Central  Google Scholar 

  • Wingender G, Kronenberg M (2008) Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation. Am J Physiol Gastrointest Liver Physiol 294:G1–G8

    Article  CAS  PubMed  Google Scholar 

  • Wingender G, Kronenberg M (2014) The role of invariant natural killer T Cells in autoimmune diseases. In: Rose NR, Mackay IR (eds) The autoimmune diseases. Fifth Edition. Elsevier, pp 103–129

  • Wingender G, Krebs P, Beutler B et al (2010) Antigen-specific cytotoxicity by invariant NKT cells in vivo is CD95/CD178-dependent and is correlated with antigenic potency. J Immunol 185:2721–2729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wingender G, Rogers P, Batzer G et al (2011) Invariant NKT cells are required for airway inflammation induced by environmental antigens. J Exp Med 208:1151–1162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wingender G, Stepniak D, Krebs P et al (2012) Intestinal microbes affect phenotypes and functions of invariant natural killer T cells in mice. Gastroenterology 143:418–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Witkin SS, Ledger WJ (2012) Complexities of the uniquely human vagina. Sci Transl Med 4:132fs11

    Article  PubMed  Google Scholar 

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Acknowledgments

The author would like to thank Drs. Duygu Sag and Alysia M. Birkholz for critical reading of the manuscript.

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  1. Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylul University Health Campus, Balcova, 35340, Izmir, Turkey

    Gerhard Wingender

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Wingender, G. From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells. Arch. Immunol. Ther. Exp. 64, 291–298 (2016). https://doi.org/10.1007/s00005-015-0381-7

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