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Purinergic signaling during intestinal inflammation

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Abstract

Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer. Aberrant purinergic signaling pathways have been implicated in disordered thromboregulation and immune dysregulation, as noted in the pathogenesis of IBD and other gastrointestinal/hepatic autoimmune diseases. Expression of CD39 on endothelial or immune cells allows for homeostatic integration of hemostasis and immunity, which are disrupted in IBD. Our focus in this review is on novel aspects of the functions of CD39 and related NTPDases in IBD. Regulated CD39 activity allows for scavenging of extracellular nucleotides, the maintenance of P2-receptor integrity and coordination of adenosinergic signaling responses. CD39 together with CD73, serves as an integral component of the immunosuppressive machinery of dendritic cells, myeloid cells, T and B cells. Genetic inheritance and environental factors closely regulate the levels of expression and phosphohydrolytic activity of CD39, both on immune cells and released microparticles. Purinergic mechanisms associated with T regulatory and supressor T helper type 17 cells modulate disease activity in IBD, as can be modeled in experimental colitis. As a recent example, upregulation of CD39 is dependent upon ligation of the aryl hydrocarbon receptor (AHR), as with natural ligands such as bilirubin and 2-(1′ H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Decreased expression of CD39 and/or dysfunctional AHR signaling, however, abrogates the protective effects of immunosuppressive AHR ligands. These factors could also serve as biomarkers of disease activity in IBD. Heightened thrombosis, inflammation, and immune disturbances as seen in IBD appear to be associated with aberrant purinergic signaling. Ongoing development of therapeutic strategies augmenting CD39 ectonucleotidase bioactivity via cytokines or AHR ligands offers promise for management of thrombophilia, disordered inflammation, and aberrant immune reactivity in IBD.

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References

  1. Eltzschig HK, Sitkovsky MV, Robson SC (2012) Purinergic signaling during inflammation. N Engl J Med 367:2322–2333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Longhi MS, Robson SC, Bernstein SH, Serra S, Deaglio S (2013) Biological functions of ecto-enzymes in regulating extracellular adenosine levels in neoplastic and inflammatory disease states. J Mol Med (Berl) 91:165–172

    Article  CAS  Google Scholar 

  3. Takenaka MC, Robson S, Quintana FJ (2016) Regulation of the T cell response by CD39. Trends Immunol 37:427–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Allard B, Longhi MS, Robson SC, Stagg J (2017) The ectonucleotidases CD39 and CD73: novel checkpoint inhibitor targets. Immunol Rev 276:121–144

    Article  CAS  PubMed  Google Scholar 

  5. Luthje J (1989) Origin, metabolism and function of extracellular adenine nucleotides in the blood [published erratum appears in Klin Wochenschr 1989 May 15;67(10):558]. [review]. Klin Wochenschr 67:317–327

    Article  CAS  PubMed  Google Scholar 

  6. Burnstock G, Knight G (2004) Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol 240:31–304

    Article  CAS  PubMed  Google Scholar 

  7. Burnstock G (2002) Purinergic signaling and vascular cell proliferation and death. Arterioscler Thromb Vasc Biol 22:364–373

    Article  PubMed  Google Scholar 

  8. Resta R, Yamashita Y, Thompson LF (1998) Ecto-enzyme and signaling functions of lymphocyte CD73. Immunol Rev 161:95–109

    Article  CAS  PubMed  Google Scholar 

  9. Robson SC, Sevigny J, Zimmermann H (2006) The E-NTPDase family of ecto-nucleotidases: structure function relationshhips and pathophysiological significance. Purinergic Signal 2:409–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Beldi G, Enjyoji K, Wu Y, Miller L, Banz Y, Sun X, Robson SC (2008) The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism. Front Biosci 13:2588–2603

    Article  PubMed  PubMed Central  Google Scholar 

  11. Horenstein AL, Chillemi A, Zaccarello G, Bruzzone S, Quarona V, Zito A, Serra S, Malavasi F (2013) A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes. Oncoimmunology 2:e26246

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cekic C, Linden J (2016) Purinergic regulation of the immune system. Nat Rev Immunol 16:177–192

    Article  CAS  PubMed  Google Scholar 

  13. Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M et al (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204:1257–1265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dwyer KM, Hanidziar D, Putheti P, Hill PA, Pommey S, McRae JL, Winterhalter A, Doherty G, Deaglio S, Koulmanda M et al (2010) Expression of CD39 by human peripheral blood CD4+ CD25+ T cells denotes a regulatory memory phenotype. Am J Transplant 10:2410–2420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cohen HB, Briggs KT, Marino JP, Ravid K, Robson SC, Mosser DM (2013) TLR stimulation initiates a CD39-based autoregulatory mechanism that limits macrophage inflammatory responses. Blood 122:1935–1945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Longhi MS, Moss A, Bai A, Wu Y, Huang H, Cheifetz A, Quintana FJ, Robson SC (2014) Characterization of human CD39+ Th17 cells with suppressor activity and modulation in inflammatory bowel disease. PLoS One 9:e87956

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jin X, Shepherd RK, Duling BR, Linden J (1997) Inosine binds to A3 adenosine receptors and stimulates mast cell degranulation. J Clin Invest 100:2849–2857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Joos G, Jakim J, Kiss B, Szamosi R, Papp T, Felszeghy S, Saghy T, Nagy G, Szondy Z (2017) Involvement of adenosine A3 receptors in the chemotactic navigation of macrophages towards apoptotic cells. Immunol Lett 183:62–72

    Article  CAS  PubMed  Google Scholar 

  19. Di Virgilio F, Boeynaems JM, Robson SC (2009) Extracellular nucleotides as negative modulators of immunity. Curr Opin Pharmacol 9:507–513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sun X, Han L, Seth P, Bian S, Li L, Csizmadia E, Junger WG, Schmelzle M, Usheva A, Tapper EB et al (2013) Disordered purinergic signaling and abnormal cellular metabolism are associated with development of liver cancer in Cd39/ENTPD1 null mice. Hepatology 57:205–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gao L, Dong L, Whitlock JP Jr (1998) A novel response to dioxin. Induction of ecto-ATPase gene expression. J Biol Chem 273:15358–15365

    Article  CAS  PubMed  Google Scholar 

  22. Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B, Laroni A, Kozoriz D, Weiner HL, Quintana FJ (2010) Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol 11:846–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mascanfroni ID, Yeste A, Vieira SM, Burns EJ, Patel B, Sloma I, Wu Y, Mayo L, Ben-Hamo R, Efroni S et al (2013) IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol 14:1054–1063

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hart ML, Gorzolla IC, Schittenhelm J, Robson SC, Eltzschig HK (2010) SP1-dependent induction of CD39 facilitates hepatic ischemic preconditioning. J Immunol 184:4017–4024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hart ML, Grenz A, Gorzolla IC, Schittenhelm J, Dalton JH, Eltzschig HK (2011) Hypoxia-inducible factor-1alpha-dependent protection from intestinal ischemia/reperfusion injury involves ecto-5′-nucleotidase (CD73) and the A2B adenosine receptor. J Immunol 186:4367–4374

    Article  CAS  PubMed  Google Scholar 

  26. Eltzschig HK, Bonney SK, Eckle T (2013) Attenuating myocardial ischemia by targeting A2B adenosine receptors. Trends Mol Med 19:345–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eckle T, Hartmann K, Bonney S, Reithel S, Mittelbronn M, Walker LA, Lowes BD, Han J, Borchers CH, Buttrick PM et al (2012) Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia. Nat Med 18:774–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Perez-Aso M, Feig JL, Mediero A, Cronstein BN (2013) Adenosine A2A receptor and TNF-alpha regulate the circadian machinery of the human monocytic THP-1 cells. Inflammation 36:152–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Stein AC, Gaetano JN, Jacobs J, Kunnavakkam R, Bissonnette M, Pekow J (2016) Northern latitude but not season is associated with increased rates of hospitalizations related to inflammatory bowel disease: results of a multi-year analysis of a national cohort. PLoS One 11:e0161523

    Article  PubMed  PubMed Central  Google Scholar 

  30. Palmieri O, Mazzoccoli G, Bossa F, Maglietta R, Palumbo O, Ancona N, Corritore G, Latiano T, Martino G, Rubino R et al (2015) Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome. Chronobiol Int 32:903–916

    Article  PubMed  Google Scholar 

  31. Jangi S, Otterbein L, Robson S (2013) The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int J Biochem Cell Biol 45:2843–2851

    Article  CAS  PubMed  Google Scholar 

  32. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453:65–71

    Article  CAS  PubMed  Google Scholar 

  33. Goettel JA, Gandhi R, Kenison JE, Yeste A, Murugaiyan G, Sambanthamoorthy S, Griffith AE, Patel B, Shouval DS, Weiner HL et al (2016) AHR activation is protective against colitis driven by T cells in humanized mice. Cell Rep 17:1318–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Naganuma M, Wiznerowicz EB, Lappas CM, Linden J, Worthington MT, Ernst PB (2006) Cutting edge: critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol 177:2765–2769

    Article  CAS  PubMed  Google Scholar 

  35. Frick JS, MacManus CF, Scully M, Glover LE, Eltzschig HK, Colgan SP (2009) Contribution of adenosine A2B receptors to inflammatory parameters of experimental colitis. J Immunol 182:4957–4964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Doherty GA, Bai A, Hanidziar D, Longhi MS, Lawlor GO, Putheti P, Csizmadia E, Nowak M, Cheifetz AS, Moss AC et al (2012) CD73 is a phenotypic marker of effector memory Th17 cells in inflammatory bowel disease. Eur J Immunol 42:3062–3072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Friedman DJ, Kunzli BM, Yi AR, Sevigny J, Berberat PO, Enjyoji K, Csizmadia E, Friess H, Robson SC (2009) From the cover: CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proc Natl Acad Sci U S A 106:16788–16793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Orru V, Steri M, Sole G, Sidore C, Virdis F, Dei M, Lai S, Zoledziewska M, Busonero F, Mulas A et al (2013) Genetic variants regulating immune cell levels in health and disease. Cell 155:242–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Roederer M, Quaye L, Mangino M, Beddall MH, Mahnke Y, Chattopadhyay P, Tosi I, Napolitano L, Terranova Barberio M, Menni C et al (2015) The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis. Cell 161:387–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mangino M, Roederer M, Beddall MH, Nestle FO, Spector TD (2017) Innate and adaptive immune traits are differentially affected by genetic and environmental factors. Nat Commun 8:13850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mitsuhashi S, Feldbrugge L, Csizmadia E, Mitsuhashi M, Robson SC, Moss AC (2016) Luminal extracellular vesicles (EVs) in inflammatory bowel disease (IBD) exhibit proinflammatory effects on epithelial cells and macrophages. Inflamm Bowel Dis 22:1587–1595

    Article  PubMed  PubMed Central  Google Scholar 

  42. Jiang ZG, Wu Y, Csizmadia E, Feldbrugge L, Enjyoji K, Tigges J, Toxavidis V, Stephan H, Muller CE, McKnight CJ et al (2014) Characterization of circulating microparticle-associated CD39 family ecto-nucleotidases in human plasma. Purinergic Signal. doi:10.1007/s11302-014-9423-6

  43. Banz Y, Beldi G, Wu Y, Atkinson B, Usheva A, Robson SC (2008) CD39 is incorporated into plasma microparticles where it maintains functional properties and impacts endothelial activation. Br J Haematol 142:627–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Haller CA, Cui W, Wen J, Robson SC, Chaikof EL (2006) Reconstitution of CD39 in liposomes amplifies nucleoside triphosphate diphosphohydrolase activity and restores thromboregulatory properties. J Vasc Surg 43:816–823

    Article  PubMed  Google Scholar 

  45. Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T et al (2015) Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 163:367–380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Atarashi K, Nishimura J, Shima T, Umesaki Y, Yamamoto M, Onoue M, Yagita H, Ishii N, Evans R, Honda K et al (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455:808–812

    Article  CAS  PubMed  Google Scholar 

  47. Baron L, Gombault A, Fanny M, Villeret B, Savigny F, Guillou N, Panek C, Le Bert M, Lagente V, Rassendren F et al (2015) The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine. Cell Death Dis 6:e1629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ouyang X, Ghani A, Malik A, Wilder T, Colegio OR, Flavell RA, Cronstein BN, Mehal WZ (2013) Adenosine is required for sustained inflammasome activation via the A(2)A receptor and the HIF-1alpha pathway. Nat Commun 4:2909

    PubMed  PubMed Central  Google Scholar 

  49. Wang Y, Telesford KM, Ochoa-Reparaz J, Haque-Begum S, Christy M, Kasper EJ, Wang L, Wu Y, Robson SC, Kasper DL et al (2014) An intestinal commensal symbiosis factor controls neuroinflammation via TLR2-mediated CD39 signalling. Nat Commun 5:4432

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Sansom FM, Robson SC, Hartland EL (2008) Possible effects of microbial ecto-nucleoside triphosphate diphosphohydrolases on host-pathogen interactions. Microbiol Mol Biol Rev 72:765–781 table of contents

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Vaughn BP, Vatanen T, Allegretti JR, Bai A, Xavier RJ, Korzenik J, Gevers D, Ting A, Robson SC, Moss AC (2016) Increased intestinal microbial diversity following fecal microbiota transplant for active Crohn’s disease. Inflamm Bowel Dis 22:2182–2190

    Article  PubMed  Google Scholar 

  52. Chiaro TR, Soto R, Zac Stephens W, Kubinak JL, Petersen C, Gogokhia L, Bell R, Delgado JC, Cox J, Voth W et al (2017) A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice. Sci Transl Med 9

  53. Sivignon A, de Vallee A, Barnich N, Denizot J, Darcha C, Pignede G, Vandekerckove P, Darfeuille-Michaud A (2015) Saccharomyces cerevisiae CNCM I-3856 prevents colitis induced by AIEC bacteria in the transgenic mouse model mimicking Crohn’s disease. Inflamm Bowel Dis 21:276–286

    Article  PubMed  Google Scholar 

  54. Lavoie EG, Gulbransen BD, Martin-Satue M, Aliagas E, Sharkey KA, Sevigny J (2011) Ectonucleotidases in the digestive system: focus on NTPDase3 localization. Am J Physiol Gastrointest Liver Physiol 300:G608–G620

    Article  CAS  PubMed  Google Scholar 

  55. Kusu T, Kayama H, Kinoshita M, Jeon SG, Ueda Y, Goto Y, Okumura R, Saiga H, Kurakawa T, Ikeda K et al (2013) Ecto-nucleoside triphosphate diphosphohydrolase 7 controls Th17 cell responses through regulation of luminal ATP in the small intestine. J Immunol 190:774–783

    Article  CAS  PubMed  Google Scholar 

  56. Zimmermann H, Zebisch M, Strater N (2012) Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal 8:437–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Heine P, Braun N, Heilbronn A, Zimmermann H (1999) Functional characterization of rat ecto-ATPase and ecto-ATP diphosphohydrolase after heterologous expression in CHO cells. Eur J Biochem 262:102–107

    Article  CAS  PubMed  Google Scholar 

  58. Shi JD, Kukar T, Wang CY, Li QZ, Cruz PE, Davoodi-Semiromi A, Yang P, Gu Y, Lian W, Wu DH et al (2001) Molecular cloning and characterization of a novel mammalian endo-apyrase (LALP1). J Biol Chem 276:17474–17478

    Article  CAS  PubMed  Google Scholar 

  59. Wink MR, Braganhol E, Tamajusuku AS, Lenz G, Zerbini LF, Libermann TA, Sevigny J, Battastini AM, Robson SC (2006) Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes. Neuroscience 138:421–432

    Article  CAS  PubMed  Google Scholar 

  60. Belcher SM, Zsarnovszky A, Crawford PA, Hemani H, Spurling L, Kirley TL (2006) Immunolocalization of ecto-nucleoside triphosphate diphosphohydrolase 3 in rat brain: implications for modulation of multiple homeostatic systems including feeding and sleep-wake behaviors. Neuroscience 137:1331–1346

    Article  CAS  PubMed  Google Scholar 

  61. Cardoso AM, Schetinger MR, Correia-de-Sa P, Sevigny J (2015) Impact of ectonucleotidases in autonomic nervous functions. Auton Neurosci 191:25–38

    Article  CAS  PubMed  Google Scholar 

  62. Braun N, Sevigny J, Robson SC, Hammer K, Hanani M, Zimmermann H (2004) Association of the ecto-ATPase NTPDase2 with glial cells of the peripheral nervous system. Glia 45:124–132

    Article  PubMed  Google Scholar 

  63. Di Giovangiulio M, Verheijden S, Bosmans G, Stakenborg N, Boeckxstaens GE, Matteoli G (2015) The neuromodulation of the intestinal immune system and its relevance in inflammatory bowel disease. Front Immunol 6:590

    Article  PubMed  PubMed Central  Google Scholar 

  64. Gabanyi I, Muller PA, Feighery L, Oliveira TY, Costa-Pinto FA, Mucida D (2016) Neuro-immune interactions drive tissue programming in intestinal macrophages. Cell 164:378–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Gallego D, Gil V, Martinez-Cutillas M, Mane N, Martin MT, Jimenez M (2012) Purinergic neuromuscular transmission is absent in the colon of P2Y(1) knocked out mice. J Physiol 590:1943–1956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Galligan JJ (2002) Ligand-gated ion channels in the enteric nervous system. Neurogastroenterol Motil 14:611–623

    Article  CAS  PubMed  Google Scholar 

  67. Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, Muruve DA, McKay DM, Beck PL, Mawe GM et al (2012) Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis. Nat Med 18:600–604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gombault A, Baron L, Couillin I (2012) ATP release and purinergic signaling in NLRP3 inflammasome activation. Front Immunol 3:414

    PubMed  Google Scholar 

  69. Fields RD, Stevens B (2000) ATP: an extracellular signaling molecule between neurons and glia. Trends Neurosci 23:625–633

    Article  CAS  PubMed  Google Scholar 

  70. Ruhl A (2005) Glial cells in the gut. Neurogastroenterol Motil 17:777–790

    Article  CAS  PubMed  Google Scholar 

  71. Brown IA, McClain JL, Watson RE, Patel BA, Gulbransen BD (2016) Enteric glia mediate neuron death in colitis through purinergic pathways that require connexin-43 and nitric oxide. Cell Mol Gastroenterol Hepatol 2:77–91

    Article  PubMed  Google Scholar 

  72. Eltzschig HK, Bratton DL, Colgan SP (2014) Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases. Nat Rev Drug Discov 13:852–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ochoa-Cortes F, Linan-Rico A, Jacobson KA, Christofi FL (2014) Potential for developing purinergic drugs for gastrointestinal diseases. Inflamm Bowel Dis 20:1259–1287

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work summarized in this review article was supported by the National Institute of Health grants to SCR and MSL; R01 HL094400; R01 DK108894; P01HL107152, and P01 HL087203 as well as the generosity of the family of Jane O. Siegel; as well as a Clinical Research Award from the American Gastroenterology Association and the Alan Holfman Clinical and Translational Research Award from the American Association for the Study of Liver Disease to ZGJ. We thank Eliza Robson for the graphic design for figures.

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  1. Division of Gastroenterology and Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, C/O E/CLS 612, 3 Blackfan Circle, Boston, MA, 02215, USA

    Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang & Simon C. Robson

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  1. Maria Serena Longhi
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Longhi, M.S., Moss, A., Jiang, Z.G. et al. Purinergic signaling during intestinal inflammation. J Mol Med 95, 915–925 (2017). https://doi.org/10.1007/s00109-017-1545-1

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