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Cited by 79Immunotherapy and Immune ResponsesParasites and Host InteractionsImmune Response and Inflammation

Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses

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Kaisar, Maria M. M., Ritter, Manuel, del Fresno, Carlos, Jónasdóttir, Hulda S., van der Ham, Alwin J., Pelgrom, Leonard R., Schramm, Gabriele, Layland, Laura E. +5 more·2018·PLOS Biology
DOI 10.1371/journal.pbio.2005504PMC PMC5927467
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Abstract

The molecular mechanisms through which dendritic cells (DCs) prime T helper 2 (Th2) responses, including those elicited by parasitic helminths, remain incompletely understood. Here, we report that soluble egg antigen (SEA) from Schistosoma mansoni, which is well known to drive potent Th2 responses, triggers DCs to produce prostaglandin E2 (PGE2), which subsequently-in an autocrine manner-induces OX40 ligand (OX40L) expression to license these DCs to drive Th2 responses. Mechanistically, SEA was found to promote PGE2 synthesis through Dectin-1 and Dectin-2, and via a downstream signaling cascade involving spleen tyrosine kinase (Syk), extracellular signal-regulated kinase (ERK), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase 1 and 2 (COX-1 and COX-2). In addition, this pathway was activated independently of the actions of omega-1 (ω-1), a previously described Th2-priming glycoprotein present in SEA. These findings were supported by in vivo murine data showing that ω-1-independent Th2 priming by SEA was mediated by Dectin-2 and Syk signaling in DCs. Finally, we found that Dectin-2-/-, and to a lesser extent Dectin-1-/- mice, displayed impaired Th2 responses and reduced egg-driven granuloma formation following S. mansoni infection, highlighting the physiological importance of this pathway in Th2 polarization during a helminth infection. In summary, we identified a novel pathway in DCs involving Dectin-1/2-Syk-PGE2-OX40L through which Th2 immune responses are induced.

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  1. [1]Gause WC, Wynn TA, Allen JE (2013) Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nat Rev Immunol 13: 607– 614. doi: 10.1038/nri3476 23827958 PMC3789590 · DOI
  2. [2]Kapsenberg ML (2003) Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 3: 984– 993. doi: 10.1038/nri1246 14647480 · DOI
  3. [3]de Jong EC, Vieira PL, Kalinski P, Schuitemaker JH, Tanaka Y, et al (2002) Microbial compounds selectively induce Th1 cell-promoting or Th2 cell-promoting dendritic cells in vitro with diverse th cell-polarizing signals. J Immunol 168: 1704– 1709. 11823500
  4. [4]Connor LM, Tang SC, Camberis M, Le Gros G, Ronchese F (2014) Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo. J Immunol 193: 2709– 2717. doi: 10.4049/jimmunol.1400374 25108019 · DOI
  5. [5]Cook PC, Jones LH, Jenkins SJ, Wynn TA, Allen JE, et al (2012) Alternatively activated dendritic cells regulate CD4+ T-cell polarization in vitro and in vivo. Proc Natl Acad Sci U S A 109: 9977– 9982. doi: 10.1073/pnas.1121231109 22660926 PMC3382483 · DOI
  6. [6]Everts B, Adegnika AA, Kruize YC, Smits HH, Kremsner PG, et al (2010) Functional impairment of human myeloid dendritic cells during Schistosoma haematobium infection. PLoS Negl Trop Dis 4: e667 doi: 10.1371/journal.pntd.0000667 20422029 PMC2857749 · DOI
  7. [7]Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med 173: 159– 166. 1824635 PMC2118762
  8. [8]Pearce EJ, MacDonald AS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2: 499– 511. doi: 10.1038/nri843 12094224 · DOI
  9. [9]Everts B, Hussaarts L, Driessen NN, Meevissen MH, Schramm G, et al (2012) Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor. J Exp Med 209: 1753– 1767, s1751. doi: 10.1084/jem.20111381 22966004 PMC3457738 · DOI · Paper page
  10. [10]Hussaarts L, Smits HH, Schramm G, van der Ham AJ, van der Zon GC, et al (2013) Rapamycin and omega-1: mTOR-dependent and -independent Th2 skewing by human dendritic cells. Immunol Cell Biol 91: 486– 489. doi: 10.1038/icb.2013.31 23835553 · DOI
  11. [11]Jankovic D, Steinfelder S, Kullberg MC, Sher A (2006) Mechanisms underlying helminth- induced Th2 polarization: default, negative or positive pathways? Chem Immunol Allergy 90: 65– 81. doi: 10.1159/000088881 16210903 · DOI
  12. [12]Klaver EJ, Kuijk LM, Lindhorst TK, Cummings RD, van Die I (2015) Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor. PLoS ONE 10: e0124089 doi: 10.1371/journal.pone.0124089 25897665 PMC4405200 · DOI
  13. [13]van Liempt E, van Vliet SJ, Engering A, Garcia Vallejo JJ, Bank CM, et al (2007) Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation. Mol Immunol 44: 2605– 2615. doi: 10.1016/j.molimm.2006.12.012 17241663 · DOI
  14. [14]Fitzsimmons CM, Schramm G, Jones FM, Chalmers IW, Hoffmann KF, et al (2005) Molecular characterization of omega-1: a hepatotoxic ribonuclease from Schistosoma mansoni eggs. Mol Biochem Parasitol 144: 123– 127. doi: 10.1016/j.molbiopara.2005.08.003 16143411 · DOI
  15. [15]Steinfelder S, Andersen JF, Cannons JL, Feng CG, Joshi M, et al (2009) The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1). J Exp Med 206: 1681– 1690. doi: 10.1084/jem.20082462 19635859 PMC2722182 · DOI
  16. [16]Dunne DW, Jones FM, Doenhoff MJ (1991) The purification, characterization, serological activity and hepatotoxic properties of two cationic glycoproteins (alpha 1 and omega 1) from Schistosoma mansoni eggs. Parasitology 103 Pt 2: 225– 236. 1745548
  17. [17]Cass CL, Johnson JR, Califf LL, Xu T, Hernandez HJ, et al (2007) Proteomic analysis of Schistosoma mansoni egg secretions. Mol Biochem Parasitol 155: 84– 93. doi: 10.1016/j.molbiopara.2007.06.002 17644200 PMC2077830 · DOI
  18. [18]Mathieson W, Wilson RA (2010) A comparative proteomic study of the undeveloped and developed Schistosoma mansoni egg and its contents: the miracidium, hatch fluid and secretions. Int J Parasitol 40: 617– 628. doi: 10.1016/j.ijpara.2009.10.014 19917288 · DOI
  19. [19]Hagen J, Young ND, Every AL, Pagel CN, Schnoeller C, et al (2014) Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo. Nat Commun 5: 5375 doi: 10.1038/ncomms6375 25400038 PMC4243216 · DOI
  20. [20]Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, et al (2009) Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med 206: 1673– 1680. doi: 10.1084/jem.20082460 19635864 PMC2722183 · DOI
  21. [21]Harizi H (2013) The immunobiology of prostanoid receptor signaling in connecting innate and adaptive immunity. Biomed Res Int 2013: 683405 doi: 10.1155/2013/683405 24024207 PMC3762073 · DOI
  22. [22]Hirata T, Narumiya S (2012) Prostanoids as regulators of innate and adaptive immunity. Adv Immunol 116: 143– 174. doi: 10.1016/B978-0-12-394300-2.00005-3 23063076 · DOI
  23. [23]Dalli J, Serhan CN (2012) Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood 120: e60– 72. doi: 10.1182/blood-2012-04-423525 22904297 PMC3471524 · DOI
  24. [24]Sreeramkumar V, Fresno M, Cuesta N (2012) Prostaglandin E2 and T cells: friends or foes? Immunol Cell Biol 90: 579– 586. doi: 10.1038/icb.2011.75 21946663 PMC3389798 · DOI
  25. [25]Giera M, Kaisar MMM, Derks RJE, Steenvoorden E, Kruize YCM, et al (2017) The Schistosoma mansoni lipidome: Leads for immunomodulation. Analytica Chimica Acta. 30292284
  26. [26]Flynn S, Toellner KM, Raykundalia C, Goodall M, Lane P (1998) CD4 T cell cytokine differentiation: the B cell activation molecule, OX40 ligand, instructs CD4 T cells to express interleukin 4 and upregulates expression of the chemokine receptor, Blr-1. J Exp Med 188: 297– 304. 9670042 PMC2212448
  27. [27]Krause P, Bruckner M, Uermosi C, Singer E, Groettrup M, et al (2009) Prostaglandin E(2) enhances T-cell proliferation by inducing the costimulatory molecules OX40L, CD70, and 4-1BBL on dendritic cells. Blood 113: 2451– 2460. doi: 10.1182/blood-2008-05-157123 19029446 · DOI
  28. [28]Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, et al (2005) TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med 202: 1213– 1223. doi: 10.1084/jem.20051135 16275760 PMC2213234 · DOI · Paper page
  29. [29]Zelle-Rieser C, Ramoner R, Artner-Dworzak E, Casari A, Bartsch G, et al (2002) Human monocyte-derived dendritic cells are deficient in prostaglandin E2 production. FEBS Lett 511: 123– 126. 11821061
  30. [30]Rey A, Quartulli F, Escoubet L, Sozzani P, Caput D, et al (1999) IL-13 induces serine phosphorylation of cPLA2 in mouse peritoneal macrophages leading to arachidonic acid and PGE2 production and blocks the zymosan-induced serine phosphorylation of cPLA2 and eicosanoid production. Biochim Biophys Acta 1440: 183– 193. 10521702
  31. [31]van Riet E, Everts B, Retra K, Phylipsen M, van Hellemond JJ, et al (2009) Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization. BMC Immunol 10: 9 doi: 10.1186/1471-2172-10-9 19193240 PMC2672924 · DOI
  32. [32]Milella M, Gismondi A, Roncaioli P, Bisogno L, Palmieri G, et al (1997) CD16 cross-linking induces both secretory and extracellular signal-regulated kinase (ERK)-dependent cytosolic phospholipase A2 (PLA2) activity in human natural killer cells: involvement of ERK, but not PLA2, in CD16-triggered granule exocytosis. J Immunol 158: 3148– 3154. 9120268
  33. [34]van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, et al (2003) The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology 13: 471– 478. doi: 10.1093/glycob/cwg052 12626400 · DOI · Paper page
  34. [35]Ferguson BJ, Newland SA, Gibbs SE, Tourlomousis P, Fernandes dos Santos P, et al (2015) The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1beta secretion in macrophages. Int J Parasitol 45: 809– 813. doi: 10.1016/j.ijpara.2015.08.005 26385440 · DOI
  35. [36]Saijo S, Iwakura Y (2011) Dectin-1 and Dectin-2 in innate immunity against fungi. Int Immunol 23: 467– 472. doi: 10.1093/intimm/dxr046 21677049 · DOI
  36. [37]Hangai S, Ao T, Kimura Y, Matsuki K, Kawamura T, et al (2016) PGE2 induced in and released by dying cells functions as an inhibitory DAMP. Proc Natl Acad Sci U S A 113: 3844– 3849. doi: 10.1073/pnas.1602023113 27001836 PMC4833254 · DOI
  37. [38]Carvalho A, Giovannini G, De Luca A, D'Angelo C, Casagrande A, et al (2012) Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis. Cell Mol Immunol 9: 276– 286. doi: 10.1038/cmi.2012.1 22543832 PMC4012853 · DOI
  38. [39]Smeekens SP, van de Veerdonk FL, van der Meer JW, Kullberg BJ, Joosten LA, et al (2010) The Candida Th17 response is dependent on mannan- and beta-glucan-induced prostaglandin E2. Int Immunol 22: 889– 895. doi: 10.1093/intimm/dxq442 21059767 · DOI
  39. [40]Noverr MC, Erb-Downward JR, Huffnagle GB (2003) Production of eicosanoids and other oxylipins by pathogenic eukaryotic microbes. Clin Microbiol Rev 16: 517– 533. doi: 10.1128/CMR.16.3.517-533.2003 12857780 PMC164223 · DOI
  40. [41]Brose SA, Thuen BT, Golovko MY (2011) LC/MS/MS method for analysis of E(2) series prostaglandins and isoprostanes. J Lipid Res 52: 850– 859. doi: 10.1194/jlr.D013441 21317107 PMC3284174 · DOI
  41. [42]Milne GL, Yin H, Hardy KD, Davies SS, Roberts LJ 2nd (2011) Isoprostane generation and function. Chem Rev 111: 5973– 5996. doi: 10.1021/cr200160h 21848345 PMC3192249 · DOI
  42. [43]Abdel Baset H, O'Neill GP, Ford-Hutchinson AW (1995) Characterization of arachidonic-acid-metabolizing enzymes in adult Schistisoma mansoni. Mol Biochem Parasitol 73: 31– 41. 8577345
  43. [44]Ramaswamy K, Kumar P, He YX (2000) A role for parasite-induced PGE2 in IL-10-mediated host immunoregulation by skin stage schistosomula of Schistosoma mansoni. J Immunol 165: 4567– 4574. 11035098
  44. [45]Agrawal K, Kale SL, Arora N (2015) Protease activity of Per a 10 potentiates Th2 polarization by increasing IL-23 and OX40L. Eur J Immunol 45: 3375– 3385. doi: 10.1002/eji.201545734 26417883 · DOI
  45. [46]Hoshino A, Tanaka Y, Akiba H, Asakura Y, Mita Y, et al (2003) Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma. Eur J Immunol 33: 861– 869. doi: 10.1002/eji.200323455 12672051 · DOI
  46. [47]Barrett NA, Maekawa A, Rahman OM, Austen KF, Kanaoka Y (2009) Dectin-2 recognition of house dust mite triggers cysteinyl leukotriene generation by dendritic cells. J Immunol 182: 1119– 1128. 19124755 PMC3682801
  47. [48]Barrett NA, Rahman OM, Fernandez JM, Parsons MW, Xing W, et al (2011) Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes. J Exp Med 208: 593– 604. doi: 10.1084/jem.20100793 21357742 PMC3058587 · DOI
  48. [49]Zhu LL, Zhao XQ, Jiang C, You Y, Chen XP, et al (2013) C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection. Immunity 39: 324– 334. doi: 10.1016/j.immuni.2013.05.017 23911656 · DOI
  49. [50]Rodriguez M, Domingo E, Municio C, Alvarez Y, Hugo E, et al (2014) Polarization of the innate immune response by prostaglandin E2: a puzzle of receptors and signals. Mol Pharmacol 85: 187– 197. doi: 10.1124/mol.113.089573 24170779 · DOI
  50. [51]Suram S, Brown GD, Ghosh M, Gordon S, Loper R, et al (2006) Regulation of cytosolic phospholipase A2 activation and cyclooxygenase 2 expression in macrophages by the beta-glucan receptor. J Biol Chem 281: 5506– 5514. doi: 10.1074/jbc.M509824200 16407295 · DOI
  51. [52]Smit CH, van Diepen A, Nguyen DL, Wuhrer M, Hoffmann KF, et al (2015) Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs. Mol Cell Proteomics 14: 1750– 1769. doi: 10.1074/mcp.M115.048280 25883177 PMC4587318 · DOI
  52. [53]Rogers NC, Slack EC, Edwards AD, Nolte MA, Schulz O, et al (2005) Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22: 507– 517. doi: 10.1016/j.immuni.2005.03.004 15845454 · DOI
  53. [54]Joo H, Upchurch K, Zhang W, Ni L, Li D, et al (2015) Opposing Roles of Dectin-1 Expressed on Human Plasmacytoid Dendritic Cells and Myeloid Dendritic Cells in Th2 Polarization. J Immunol 195: 1723– 1731. doi: 10.4049/jimmunol.1402276 26123355 PMC4530104 · DOI
  54. [55]Zhao Y, Chu X, Chen J, Wang Y, Gao S, et al (2016) Dectin-1-activated dendritic cells trigger potent antitumour immunity through the induction of Th9 cells. Nat Commun 7: 12368 doi: 10.1038/ncomms12368 27492902 PMC4980454 · DOI
  55. [56]Mnich SJ, Veenhuizen AW, Monahan JB, Sheehan KC, Lynch KR, et al (1995) Characterization of a monoclonal antibody that neutralizes the activity of prostaglandin E2. J Immunol 155: 4437– 4444. 7594605
  56. [57]Fischer M, Muller JP, Spies-Weisshart B, Grafe C, Kurzai O, et al (2017) Isoform localization of Dectin-1 regulates the signaling quality of anti-fungal immunity. Eur J Immunol. 28303575
  57. [58]Guasconi L, Chiapello LS, Masih DT (2015) Fasciola hepatica excretory-secretory products induce CD4+T cell anergy via selective up-regulation of PD-L2 expression on macrophages in a Dectin-1 dependent way. Immunobiology 220: 934– 939. doi: 10.1016/j.imbio.2015.02.001 25758714 · DOI
  58. [59]Clarke DL, Davis NH, Campion CL, Foster ML, Heasman SC, et al (2014) Dectin-2 sensing of house dust mite is critical for the initiation of airway inflammation. Mucosal Immunol 7: 558– 567. doi: 10.1038/mi.2013.74 24129160 PMC3998635 · DOI
  59. [60]Caton ML, Smith-Raska MR, Reizis B (2007) Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J Exp Med 204: 1653– 1664. doi: 10.1084/jem.20062648 17591855 PMC2118632 · DOI
  60. [61]Heemskerk MM, Dharuri HK, van den Berg SA, Jonasdottir HS, Kloos DP, et al (2014) Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile. J Lipid Res 55: 2532– 2540. doi: 10.1194/jlr.M051938 25320342 PMC4242446 · DOI
  61. [62]Schlegel M, Kohler D, Korner A, Granja T, Straub A, et al (2016) The neuroimmune guidance cue netrin-1 controls resolution programs and promotes liver regeneration. Hepatology 63: 1689– 1705. doi: 10.1002/hep.28347 26573873 · DOI
  62. [63]Lutz MB, Kukutsch N, Ogilvie AL, Rossner S, Koch F, et al (1999) An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods 223: 77– 92. 10037236

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Authors
Kaisar, M. M. M., Ritter, M., del Fresno, C., Jónasdóttir, H. S., van der Ham, A. J., Pelgrom, L. R., Schramm, G., Layland, L. E., Sancho, D., Prazeres da Costa, C., Giera, M., Yazdanbakhsh, M., & Everts, B.
Affiliations
  • Leiden University Medical Center (NL)
  • University Hospital Bonn (DE)
  • Research Center Borstel - Leibniz Lung Center (DE)
  • Spanish National Centre for Cardiovascular Research (ES)
Corresponding author
Everts, Bart
ORCID
Venue
PLOS Biology
Publisher
Public Library of Science (PLoS)
Published
2018-04-18
Volume
16
Issue
4
Pages
e2005504
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
DOI
10.1371/journal.pbio.2005504
PMC
PMC5927467
OpenAlex
W2802365327
Cited by
79
References
1
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FWCI
4.94
Type
journal article
Language
en
Update notices
new_version (2018-04-30)
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  • PLoS Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
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  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Leiden Repository (Leiden University) (submittedVersion)
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  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
Funders
  • European Commission (H2020, 635122)
  • Radboud Universiteit
  • Leids Universitair Medisch Centrum
  • Radboud Universitair Medisch Centrum
  • Horizon 2020 Framework Programme (635122-PROCROP H2020, 635122)
  • H2020 European Research Council (725091)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
dendritic cells, Th2 immune response, Dectin-1, Dectin-2, prostaglandin E2, autocrine signaling, OX40L, soluble egg antigen, Schistosoma mansoni, helminthiasis, Syk signaling, ERK, cyclooxygenase, granuloma formation, Th2 polarization
MeSH terms
Syk Kinase, Dectin-1, Animals, Antigens, Helminth, Cell Differentiation, Dendritic Cells, Enterotoxins, Gene Expression Regulation, Humans, Membrane Glycoproteins, Membrane Proteins, Mice, Inbred C57BL, Schistosoma mansoni, Schistosomiasis mansoni, Dinoprostone, Reactive Oxygen Species, Mice, Knockout, Th2 Cells, Autocrine Communication, MAP Kinase Signaling System, Lectins, C-Type, Tumor Necrosis Factors, Mice, Cyclooxygenase 1, Cyclooxygenase 2, OX40 Ligand, Phospholipases A2, Primary Cell Culture

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