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IL-1β limits the extent of human 6-sulfo LacNAc dendritic cell (slanDC)-mediated NK cell activation and regulates CD95-induced apoptosis

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Abstract

To function optimally, human blood natural killer (NK) cells need to communicate with other immune cells. Previously, it has been shown that NK cells communicate with 6-sulfo LacNAc dendritic cells (slanDCs), which are able to stimulate NK cells in vitro. In this study, we investigated how slanDCs regulate the level of NK cell activation. The secretion of interleukin (IL)-1β by slanDCs during coculture with NK cells increased as a result of signaling via intercellular adhesion molecule-1 on slanDCs following its interaction with lymphocyte function-associated antigen-1 on NK cells. IL-1β induced the expression of Fas receptor (CD95) on NK cells. The binding of Fas ligand (CD178) to CD95 induced the apoptosis of activated NK cells. Moreover, IL-1β also induced increased cyclooxygenase-2 expression in slanDCs, which in turn enabled the cells to secrete prostaglandin (PG)-E2. Consequently, PGE2 acted as a suppressing agent, tuning down the activation level of NK cells. In summary, IL-1β limits the level of NK cell activation by inducing apoptosis and suppression as a homeostatic regulatory function.

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References

  1. Cooper M . NK cell and DC interactions. Trends Immunol 2004; 25: 47–52.

    Article  CAS  Google Scholar 

  2. Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M et al. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 1999; 5: 405–411.

    Article  CAS  Google Scholar 

  3. Wehner R, Löbel B, Bornhäuser M, Schäkel K, Cartellieri M, Bachmann M et al. Reciprocal activating interaction between 6-sulfo LacNAc+ dendritic cells and NK cells. Int J Cancer 2009; 124: 358–366.

    Article  CAS  Google Scholar 

  4. Moretta A . Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat Rev Immunol 2002; 2: 957–964.

    Article  CAS  Google Scholar 

  5. Cooper MA, Fehniger TA, Caligiuri MA . The biology of human natural killer-cell subsets. Trends Immunol 2001; 22: 633–640.

    Article  CAS  Google Scholar 

  6. Moretta A, Bottino C, Mingari MC, Biassoni R, Moretta L . What is a natural killer cell? Nat Immunol 2002; 3: 6–8.

    Article  CAS  Google Scholar 

  7. Jacobs R, Stoll M, Stratmann G, Leo R, Link H, Schmidt RE . CD16- CD56+ natural killer cells after bone marrow transplantation. Blood 1992; 79: 3239–3244.

    CAS  PubMed  Google Scholar 

  8. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S . Functions of natural killer cells. Nat Immunol 2008; 9: 503–510.

    Article  CAS  Google Scholar 

  9. Jacobs R, Hintzen G, Kemper A, Beul K, Kempf S, Behrens G et al. CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells. Eur J Immunol 2001; 31: 3121–3127.

    Article  CAS  Google Scholar 

  10. Schäkel K, Kannagi R, Kniep B, Goto Y, Mitsuoka C, Zwirner J et al. 6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells. Immunity 2002; 17: 289–301.

    Article  Google Scholar 

  11. Schäkel K, Mayer E, Federle C, Schmitz M, Riethmüller G, Rieber EP . A novel dendritic cell population in human blood: one-step immunomagnetic isolation by a specific mAb (M-DC8) and in vitro priming of cytotoxic T lymphocytes. Eur J Immunol 1998; 28: 4084–4093.

    Article  Google Scholar 

  12. Schmitz M, Zhao S, Deuse Y, Schäkel K, Wehner R, Wöhner H et al. Tumoricidal potential of native blood dendritic cells: direct tumor cell killing and activation of NK cell-mediated cytotoxicity. J Immunol 2005; 174: 4127–4134.

    Article  CAS  Google Scholar 

  13. Tufa DM, Chatterjee D, Low HZ, Schmidt RE, Jacobs R . TNFR2 and IL-12 coactivation enables slanDCs to support NK-cell function via membrane-bound TNF-α. Eur J Immunol 2014; 44: 3717–3728.

    Article  CAS  Google Scholar 

  14. Jähnisch H, Wehner R, Tunger A, Kunze A, Oehrl S, Schäkel K et al. TLR7/8 agonists trigger immunostimulatory properties of human 6-sulfo LacNAc dendritic cells. Cancer Lett 2013; 335: 119–127.

    Article  Google Scholar 

  15. Schäkel K, von Kietzell M, Hänsel A, Ebling A, Schulze L, Haase M et al. Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes. Immunity 2006; 24: 767–777.

    Article  Google Scholar 

  16. Shrikant P, Benos DJ, Tang LP, Benveniste EN . HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells. J Immunol 1996; 156: 1307–1314.

    CAS  PubMed  Google Scholar 

  17. Etienne-manneville S, Chaverot N, Donny A . ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF- α secretion. J Immunol 1999; 163: 668–674.

    CAS  PubMed  Google Scholar 

  18. Smith A, Stanley P, Jones K, Svensson L, McDowall A, Hogg N . The role of the integrin LFA‐1 in T‐lymphocyte migration. Immunol Rev 2007; 218: 135–146.

    Article  CAS  Google Scholar 

  19. Bose TO, Pham Q-M, Jellison ER, Mouries J, Ballantyne CM, Lefrançois L . CD11a regulates effector CD8 T cell differentiation and central memory development in response to infection with Listeria monocytogenes. Infect Immun 2013; 81: 1140–1151.

    Article  CAS  Google Scholar 

  20. Lebedeva T, Dustin ML, Sykulev Y . ICAM-1 co-stimulates target cells to facilitate antigen presentation. Curr Opin Immunol 2005; 17: 251–258.

    Article  CAS  Google Scholar 

  21. Dinarello CA . Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 2009; 27: 519–550.

    Article  CAS  Google Scholar 

  22. Mayer-Barber KD, Barber DL, Shenderov K, White SD, Wilson MS, Cheever A et al. Caspase-1 independent IL-1beta production is critical for host resistance to mycobacterium tuberculosis and does not require TLR signaling in vivo. J Immunol 2010; 184: 3326–3330.

    Article  CAS  Google Scholar 

  23. Jayaraman P, Sada-Ovalle I, Nishimura T, Anderson AC, Kuchroo VK, Remold HG et al. IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. J Immunol 2013; 190: 4196–4204.

    Article  CAS  Google Scholar 

  24. Doitsh G, Galloway NLK, Geng X, Yang Z, Monroe KM, Zepeda O et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 2014; 505: 509–514.

    Article  CAS  Google Scholar 

  25. Simmons D, Botting R, Hla T . Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 2004; 56: 387–437.

    Article  CAS  Google Scholar 

  26. Harizi H . Reciprocal crosstalk between dendritic cells and natural killer cells under the effects of PGE2 in immunity and immunopathology. Cell Mol Immunol 2013; 10: 213–221.

    Article  CAS  Google Scholar 

  27. Chatterjee D, Marquardt N, Tufa D, Beauclair G, Low H, Hatlapatka T et al. Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity. Cell Commun Signal 2014; 12: 63.

    Article  Google Scholar 

  28. Van Elssen CHMJ, Vanderlocht J, Oth T, Senden-Gijsbers BLMG, Germeraad WT V, Bos GMJ . Inflammation restraining effects of prostaglandin E2 on natural killer–dendritic cell (NK-DC) interaction are imprinted during DC maturation. Blood 2011; 118: 2473–2482.

    Article  CAS  Google Scholar 

  29. Müller C, Tufa DM, Chatterjee D, Mühlradt PF, Schmidt RE, Jacobs R . The TLR-2/TLR-6 agonist macrophage-activating lipopeptide-2 augments human NK cell cytotoxicity when PGE2 production by monocytes is inhibited by a COX-2 blocker. Cancer Immunol Immunother 2015; 64: 1175–1184.

    Article  Google Scholar 

  30. McDonald PP, Bald A, Cassatella MA . Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils. Blood 1997; 89: 3421–3433.

    CAS  PubMed  Google Scholar 

  31. Newton K, Dixit VM . Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 2012; 4: a006049.

    Article  Google Scholar 

  32. Costantini C, Calzetti F, Perbellini O, Micheletti A, Scarponi C, Lonardi S et al. Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFN{gamma}: role of CD18, ICAM-1, and ICAM-3. Blood 2011; 117: 1677–1686.

    Article  CAS  Google Scholar 

  33. Rissoan CR, Soumelis V, Kadowaki N, Grouard G, Briere F, de Malefyt RW et al. Reciprocal control of T helper cell and dendritic cell differentiation. Science 1999; 283: 1183–1186.

    Article  CAS  Google Scholar 

  34. Münz C, Steinman RM, Fujii S . Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity. J Exp Med 2005; 202: 203–207.

    Article  Google Scholar 

  35. Moretta L, Ferlazzo G, Bottino C, Vitale M, Pende D, Mingari MC et al. Effector and regulatory events during natural killer-dendritic cell interactions. Immunol Rev 2006; 214: 219–228.

    Article  CAS  Google Scholar 

  36. Borg C, Jalil A, Laderach D, Maruyama K, Wakasugi H, Charrier S et al. NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs. Blood 2004; 104: 3267–3275.

    Article  CAS  Google Scholar 

  37. Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman RM, Münz C . Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 2002; 195: 343–351.

    Article  CAS  Google Scholar 

  38. Krammer PH . CD95’s deadly mission in the immune system. Nature 2000; 407: 789–795.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the cell sorting core facility at Hannover Medical School for their support. The Institute of Transfusion Medicine at Hannover Medical School has provided blood samples from healthy donors. We thank Penelope Charlotte Kay-Fedorov for thoroughly reading and improving the manuscript. This study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG): SFB738/A5, Deutsche Zentrum für Infektionsforschung (DZIF): TTU 04.802, Hannover Biomedical Research School (HBRS), REBIRTH Cluster of Excellence and Niedersächsische Krebsgesellschaft e.V.

Author contributions

DMT, FA, DC, GA and RJ performed experiments and discussed the data; DMT, FA and RJ analyzed the results and made the figures; DMT, RJ and RES designed the research; DMT wrote the manuscript.

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Author notes

  1. Dejene Milkessa Tufa and Fareed Ahmad: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, 30625, Germany

    Dejene Milkessa Tufa, Fareed Ahmad, Debanjana Chatterjee, Gerrit Ahrenstorf, Reinhold Ernst Schmidt & Roland Jacobs

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  1. Dejene Milkessa Tufa
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  2. Fareed Ahmad
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  3. Debanjana Chatterjee
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  4. Gerrit Ahrenstorf
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  5. Reinhold Ernst Schmidt
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  6. Roland Jacobs
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Correspondence to Roland Jacobs.

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Tufa, D., Ahmad, F., Chatterjee, D. et al. IL-1β limits the extent of human 6-sulfo LacNAc dendritic cell (slanDC)-mediated NK cell activation and regulates CD95-induced apoptosis. Cell Mol Immunol 14, 976–985 (2017). https://doi.org/10.1038/cmi.2016.17

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