IL-23-producing IL-10Rα-deficient gut macrophages elicit an IL-22-driven proinflammatory epithelial cell response

Science Immunology

Volumn 4, Issue 36, 2019, Pages

  Bernshtein, Biana ^a   Curato, Caterina ^a   Ioannou, Marianna ^b   Thaiss, Christoph A ^a   Gross Vered, Mor ^a   Kolesnikov, Masha ^a   Wang, Qian ^b   David, Eyal ^a   Chappell Maor, Louise ^a   Harmelin, Alon ^a   Elinav, Eran ^a   Thakker, Paresh ^c   Papayannopoulos, Venizelos ^b   Jung, Steffen ^a  

^a WEIZMANN INSTITUTE OF SCIENCE   (Israel)

^b THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^c REGENERON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE RECEPTOR CX3CR1; INTERLEUKIN 10 RECEPTOR ALPHA; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 10 RECEPTOR; INTERLEUKIN DERIVATIVE; INTERLEUKIN-22;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; EPITHELIUM CELL; GENE MUTATION; INTESTINE CELL; MACROPHAGE FUNCTION; MALE; MOUSE; MUTANT; NEUTROPHIL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; T LYMPHOCYTE; ULCERATIVE COLITIS; WILD TYPE; ANIMAL; COLITIS; GENETICS; IMMUNOLOGY; INTESTINE; MACROPHAGE; PATHOLOGY;

ANIMALS; COLITIS; EPITHELIAL CELLS; INTERLEUKIN-23; INTERLEUKINS; INTESTINES; MACROPHAGES; MALE; MICE; NEUTROPHILS; RECEPTORS, INTERLEUKIN-10;

EID: 85068153449     PISSN: None     EISSN: 24709468     Source Type: Journal    
DOI: 10.1126/sciimmunol.aau6571     Document Type: Article

References (63)

1. T. A. Manolio, F. S. Collins, N. J. Cox, D. B. Goldstein, L. A. Hindorff, D. J. Hunter, M. I. McCarthy, E. M. Ramos, L. R. Cardon, A. Chakravarti, J. H. Cho, A. E. Guttmacher, A. Kong, L. Kruglyak, E. Mardis, C. N. Rotimi, M. Slatkin, D. Valle, A. S. Whittemore, M. Boehnke, A. G. Clark, E. E. Eichler, G. Gibson, J. L. Haines, T. F. C. Mackay, S. A. McCarroll, P. M. Visscher, Finding the missing heritability of complex diseases. Nature 461, 747-753 (2009).
2. H. Huang, M. Fang, L. Jostins, M. U. Mirkov, G. Boucher, C. A. Anderson, V. Andersen, I. Cleynen, A. Cortes, F. Crins, M. D'Amato, V. Deffontaine, J. Dmitrieva, E. Docampo, M. Elansary, K. K.-H. Farh, A. Franke, A.-S. Gori, P. Goyette, J. Halfvarson, T. Haritunians, J. Knight, I. C. Lawrance, C. W. Lees, E. Louis, R. Mariman, T. Meuwissen, M. Mni, Y. Momozawa, M. Parkes, S. L. Spain, E. Théâtre, G. Trynka, J. Satsangi, S. van Sommeren, S. Vermeire, R. J. Xavier; International Inflammatory Bowel Disease Genetics Consortium, R. K. Weersma, R. H. Duerr, C. G. Mathew, J. D. Rioux, D. P. B. McGovern, J. H. Cho, M. Georges, M. J. Daly, J. C. Barrett, Fine-mapping inflammatory bowel disease loci to single-variant resolution. Nature 547, 173-178 (2017).
3. T. Joeris, K. Müller-Luda, W. W. Agace, A. M. Mowat, Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol. 10, 845-864 (2017).
4. G. F. Sonnenberg, D. Artis, Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat. Med. 21, 698-708 (2015).
5. A. Mortha, A. Chudnovskiy, D. Hashimoto, M. Bogunovic, S. P. Spencer, Y. Belkaid, M. Merad, Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343, 1249288 (2014).
6. M. Levy, A. A. Kolodziejczyk, C. A. Thaiss, E. Elinav, Dysbiosis and the immune system. Nat. Rev. Immunol. 17, 219-232 (2017).
7. K. J. Maloy, F. Powrie, Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298-306 (2011).
8. K. Takeda, B. E. Clausen, T. Kaisho, T. Tsujimura, N. Terada, I. Förster, S. Akira, Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10, 39-49 (1999).
9. D. S. Shouval, J. Ouahed, A. Biswas, J. A. Goettel, B. H. Horwitz, C. Klein, A. M. Muise, S. B. Snapper, Interleukin 10 receptor signaling: Master regulator of intestinal mucosal homeostasis in mice and humans. Adv. Immunol. 122, 177-210 (2014).
10. G. Stelzer, I. Plaschkes, D. Oz-Levi, A. Alkelai, T. Olender, S. Zimmerman, M. Twik, F. Belinky, S. Fishilevich, R. Nudel, Y. Guan-Golan, D. Warshawsky, D. Dahary, A. Kohn, Y. Mazor, S. Kaplan, T. I. Stein, H. N. Baris, N. Rappaport, M. Safran, D. Lancet, VarElect: The phenotype-based variation prioritizer of the GeneCards Suite. BMC Genomics 17, 44 (2016).
11. S. Fishilevich, R. Nudel, N. Rappaport, R. Hadar, I. Plaschkes, T. Iny Stein, N. Rosen, A. Kohn, M. Twik, M. Safran, D. Lancet, D. Cohen, GeneHancer: Genome-wide integration of enhancers and target genes in GeneCards. Database 2017, bax028 (2017).
12. E.-O. Glocker, D. Kotlarz, K. Boztug, E. M. Gertz, A. A. Schäffer, F. Noyan, M. Perro, J. Diestelhorst, A. Allroth, D. Murugan, N. Hätscher, D. Pfeifer, K.-W. Sykora, M. Sauer, H. Kreipe, M. Lacher, R. Nustede, C. Woellner, U. Baumann, U. Salzer, S. Koletzko, N. Shah, A. W. Segal, A. Sauerbrey, S. Buderus, S. B. Snapper, B. Grimbacher, C. Klein, Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 361, 2033-2045 (2009).
13. D. S. Shouval, A. Biswas, J. A. Goettel, K. McCann, E. Conaway, N. S. Redhu, I. D. Mascanfroni, Z. Al Adham, S. Lavoie, M. Ibourk, D. D. Nguyen, J. N. Samsom, J. C. Escher, R. Somech, B. Weiss, R. Beier, L. S. Conklin, C. L. Ebens, F. G. M. S. Santos, A. R. Ferreira, M. Sherlock, A. K. Bhan, W. Müller, J. R. Mora, F. J. Quintana, C. Klein, A. M. Muise, B. H. Horwitz, S. B. Snapper, Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity 40, 706-719 (2014).
14. E. Zigmond, B. Bernshtein, G. Friedlander, C. R. Walker, S. Yona, K.-W. Kim, O. Brenner, R. Krauthgamer, C. Varol, W. Müller, S. Jung, Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40, 720-733 (2014).
15. J. MacArthur, E. Bowler, M. Cerezo, L. Gil, P. Hall, E. Hastings, H. Junkins, A. McMahon, A. Milano, J. Morales, Z. M. Pendlington, D. Welter, T. Burdett, L. Hindorff, P. Flicek, F. Cunningham, H. Parkinson, The new NHGRI-EBI catalog of published genome-wide association studies (GWAS catalog). Nucleic Acids Res. 45, D896-D901 (2017).
16. M. J. Landrum, J. M. Lee, M. Benson, G. Brown, C. Chao, S. Chitipiralla, B. Gu, J. Hart, D. Hoffman, J. Hoover, W. Jang, K. Katz, M. Ovetsky, G. Riley, A. Sethi, R. Tully, R. Villamarin-Salomon, W. Rubinstein, D. R. Maglott, ClinVar: Public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44, D862-D868 (2016).
17. Y. P. Rubtsov, J. P. Rasmussen, E. Y. Chi, J. Fontenot, L. Castelli, X. Ye, P. Treuting, L. Siewe, A. Roers, W. R. Henderson Jr., W. Müller, A. Y. Rudensky, Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28, 546-558 (2008).
18. C. L. Langrish, B. S. McKenzie, N. J. Wilson, R. de Waal Malefyt, R. A. Kastelein, D. J. Cua, IL-12 and IL-23: Master regulators of innate and adaptive immunity. Immunol. Rev. 202, 96-105 (2004).
19. S. Hue, P. Ahern, S. Buonocore, M. C. Kullberg, D. J. Cua, B. S. McKenzie, F. Powrie, K. J. Maloy, Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 203, 2473-2483 (2006).
20. M. C. Kullberg, D. Jankovic, C. G. Feng, S. Hue, P. L. Gorelick, B. S. McKenzie, D. J. Cua, F. Powrie, A. W. Cheever, K. J. Maloy, A. Sher, IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med. 203, 2485-2494 (2006).
21. P. P. Ahern, C. Schiering, S. Buonocore, M. J. Mcgeachy, D. J. Cua, K. J. Maloy, F. Powrie, Interleukin-23 drives intestinal inflammation through direct activity on T cells. Immunity 33, 279-288 (2010).
22. M. A. Kinnebrew, C. Ubeda, L. A. Zenewicz, N. Smith, R. A. Flavell, E. G. Pamer, Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection. J. Infect. Dis. 201, 534-543 (2010).
23. T. Aychek, A. Mildner, S. Yona, K.-W. Kim, N. Lampl, S. Reich-Zeliger, L. Boon, N. Yogev, A. Waisman, D. J. Cua, S. Jung, IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology. Nat. Commun. 6, 6525 (2015).
24. + mononuclear phagocytes support colitis-associated innate lymphoid cell production of IL-22. J. Exp. Med. 211, 1571-1583 (2014).
25. + monocyte/macrophages promote chronic Helicobacter hepaticus-induced intestinal inflammation through the production of IL-23. Mucosal Immunol. 9, 352-363 (2016).
26. K. Sugimoto, A. Ogawa, E. Mizoguchi, Y. Shimomura, A. Andoh, A. K. Bhan, R. S. Blumberg, R. J. Xavier, A. Mizoguchi, IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Invest. 118, 534-544 (2008).
27. L. A. Zenewicz, G. D. Yancopoulos, D. M. Valenzuela, A. J. Murphy, S. Stevens, R. A. Flavell, Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29, 947-957 (2008).
28. R. Sabat, W. Ouyang, K. Wolk, Therapeutic opportunities of the IL-22-IL-22R1 system. Nat. Rev. Drug Discov. 13, 21-38 (2014).
29. + innate lymphoid cells induce colitis via interleukin-22-dependent mechanism. Mucosal Immunol. 7, 143-154 (2014).
30. G. F. Sonnenberg, M. G. Nair, T. J. Kirn, C. Zaph, L. A. Fouser, D. Artis, Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A. J. Exp. Med. 207, 1293-1305 (2010).
31. K. Wolk, H. Mitsui, K. Witte, S. Gellrich, N. Gulati, D. Humme, E. Witte, M. Gonsior, M. Beyer, M. E. Kadin, H.-D. Volk, J. G. Krueger, W. Sterry, R. Sabat, Deficient cutaneous antibacterial competence in cutaneous T-cell lymphomas: Role of Th2-mediated biased Th17 function. Clin. Cancer Res. 20, 5507-5516 (2014).
32. A. Mizoguchi, Healing of intestinal inflammation by IL-22. Inflamm. Bowel Dis. 18, 1777-1784 (2012).
33. E. Zigmond, S. Samia-Grinberg, M. Pasmanik-Chor, E. Brazowski, O. Shibolet, Z. Halpern, C. Varol, Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury. J. Immunol. 193, 344-353 (2014).
34. R. H. Duerr, K. D. Taylor, S. R. Brant, J. D. Rioux, M. S. Silverberg, M. J. Daly, A. H. Steinhart, C. Abraham, M. Regueiro, A. Griffiths, T. Dassopoulos, A. Bitton, H. Yang, S. Targan, L. W. Datta, E. O. Kistner, L. P. Schumm, A. T. Lee, P. K. Gregersen, M. M. Barmada, J. I. Rotter, D. L. Nicolae, J. H. Cho, A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461-1463 (2006).
35. D. Yen, J. Cheung, H. Scheerens, F. Poulet, T. McClanahan, B. Mckenzie, M. A. Kleinschek, A. Owyang, J. Mattson, W. Blumenschein, E. Murphy, M. Sathe, D. J. Cua, R. A. Kastelein, D. Rennick, IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J. Clin. Invest. 116, 1310-1316 (2006).
36. Y. Zheng, D. M. Danilenko, P. Valdez, I. Kasman, J. Eastham-Anderson, J. Wu, W. Ouyang, Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445, 648-651 (2007).
37. Y. Zheng, P. A. Valdez, D. M. Danilenko, Y. Hu, S. M. Sa, Q. Gong, A. R. Abbas, Z. Modrusan, N. Ghilardi, F. J. de Sauvage, W. Ouyang, Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14, 282-289 (2008).
38. G. Eberl, S. Marmon, M.-J. Sunshine, P. D. Rennert, Y. Choi, D. R. Littman, An essential function for the nuclear receptor RORt in the generation of fetal lymphoid tissue inducer cells. Nat. Immunol. 5, 64-73 (2004).
39. N. Satoh-Takayama, N. Serafini, T. Verrier, A. Rekiki, J.-C. Renauld, G. Frankel, J. P. Di Santo, The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells. Immunity 41, 776-788 (2014).
40. F. El Marjou, K.-P. Janssen, B. H.-J. Chang, M. Li, V. Hindie, L. Chan, D. Louvard, P. Chambon, D. Metzger, S. Robine, Tissue-specific and inducible Cre-mediated recombination in the gut epithelium. Genesis 39, 186-193 (2004).
41. G. Hua, T. H. Thin, R. Feldman, A. Haimovitz-Friedman, H. Clevers, Z. Fuks, R. Kolesnick, Crypt base columnar stem cells in small intestines of mice are radioresistant. Gastroenterology 143, 1266-1276 (2012).
42. P. Thakker, M. W. Leach, W. Kuang, S. E. Benoit, J. P. Leonard, S. Marusic, IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis. J. Immunol. 178, 2589-2598 (2007).
43. C. L. Zindl, J.-F. Lai, Y. K. Lee, C. L. Maynard, S. N. Harbour, W. Ouyang, D. D. Chaplin, C. T. Weaver, IL-22-producing neutrophils contribute to antimicrobial defense and restitution of colonic epithelial integrity during colitis. Proc. Natl. Acad. Sci. U.S.A. 110, 12768-12773 (2013).
44. B. M. Fournier, C. A. Parkos, The role of neutrophils during intestinal inflammation. Mucosal Immunol. 5, 354-366 (2012).
45. J. R. Grainger, E. A. Wohlfert, I. J. Fuss, N. Bouladoux, M. H. Askenase, F. Legrand, L. Y. Koo, J. M. Brenchley, I. D. C. Fraser, Y. Belkaid, Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat. Med. 19, 713-721 (2013).
46. H. Ahlfors, P. J. Morrison, J. H. Duarte, Y. Li, J. Biro, M. Tolaini, P. Di Meglio, A. J. Potocnik, B. Stockinger, IL-22 fate reporter reveals origin and control of IL-22 production in homeostasis and infection. J. Immunol. 193, 4602-4613 (2014).
47. J. Abe, T. B. Hiyama, A. Mukaiyama, S. Son, T. Mori, S. Saito, M. Osako, J. Wolanin, E. Yamashita, T. Kondo, S. Akiyama, Atomic-scale origins of slowness in the cyanobacterial circadian clock. Science 349, 312-316 (2015).
48. N. Branzk, V. Papayannopoulos, Molecular mechanisms regulating NETosis in infection and disease. Semin. Immunopathol. 35, 513-530 (2013).
49. C. Molle, T. Zhang, L. Ysebrant de Lendonck, C. Gueydan, M. Andrianne, F. Sherer, G. Van Simaeys, P. J. Blackshear, O. Leo, S. Goriely, Tristetraprolin regulation of interleukin 23 mRNA stability prevents a spontaneous inflammatory disease. J. Exp. Med. 210, 1675-1684 (2013).
50. S. A. Brooks, P. J. Blackshear, Tristetraprolin (TTP): interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim. Biophys. Acta 1829, 666-679 (2013).
51. A. Gaba, S. I. Grivennikov, M. V. Do, D. J. Stumpo, P. J. Blackshear, M. Karin, Cutting edge: IL-10-mediated tristetraprolin induction is part of a feedback loop that controls macrophage STAT3 activation and cytokine production. J. Immunol. 189, 2089-2093 (2012).
52. B. G. Feagan, W. J. Sandborn, C. Gasink, D. Jacobstein, Y. Lang, J. R. Friedman, M. A. Blank, J. Johanns, L.-L. Gao, Y. Miao, O. J. Adedokun, B. E. Sands, S. B. Hanauer, S. Vermeire, S. Targan, S. Ghosh, W. J. de Villiers, J.-F. Colombel, Z. Tulassay, U. Seidler, B. A. Salzberg, P. Desreumaux, S. D. Lee, E. V. Loftus Jr., L. A. Dieleman, S. Katz, P. Rutgeerts; UNITI-IM-UNITI Study Group, Ustekinumab as induction and maintenance therapy for Crohn's Disease. N. Engl. J. Med. 375, 1946-1960 (2016).
53. W. J. Sandborn, C. Gasink, L.-L. Gao, M. A. Blank, J. Johanns, C. Guzzo, B. E. Sands, S. B. Hanauer, S. Targan, P. Rutgeerts, S. Ghosh, W. J. S. de Villiers, R. Panaccione, G. Greenberg, S. Schreiber, S. Lichtiger, B. G. Feagan, Ustekinumab induction and maintenance therapy in refractory Crohn's disease. N. Engl. J. Med. 367, 1519-1528 (2012).
54. S. Buonocore, P. P. Ahern, H. H. Uhlig, I. I. Ivanov, D. R. Littman, K. J. Maloy, F. Powrie, Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464, 1371-1375 (2010).
55. D. S. Shouval, L. Konnikova, A. E. Griffith, S. M. Wall, A. Biswas, L. Werner, M. Nunberg, J. Kammermeier, J. A. Goettel, R. Anand, H. Chen, B. Weiss, J. Li, A. Loizides, B. Yerushalmi, T. Yanagi, R. Beier, L. S. Conklin, C. L. Ebens, F. G. M. S. Santos, M. Sherlock, J. D. Goldsmith, D. Kotlarz, S. C. Glover, N. Shah, A. Bousvaros, H. H. Uhlig, A. M. Muise, C. Klein, S. B. Snapper, Enhanced TH17 responses in patients with IL10 receptor deficiency and infantile-onset IBD. Inflamm. Bowel Dis. 23, 1950-1961 (2017).
56. M. Xu, M. Pokrovskii, Y. Ding, R. Yi, C. Au, O. J. Harrison, C. Galan, Y. Belkaid, R. Bonneau, D. R. Littman, c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554, 373-377 (2018).
57. J. Behnsen, S. Jellbauer, C. P. Wong, R. A. Edwards, M. D. George, W. Ouyang, M. Raffatellu, The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 40, 262-273 (2014).
58. S. J. Aujla, Y. R. Chan, M. Zheng, M. Fei, D. J. Askew, D. A. Pociask, T. A. Reinhart, F. McAllister, J. Edeal, K. Gaus, S. Husain, J. L. Kreindler, P. J. Dubin, J. M. Pilewski, M. M. Myerburg, C. A. Mason, Y. Iwakura, J. K. Kolls, IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med. 14, 275-281 (2008).
59. T. P. Vogel, J. D. Milner, M. A. Cooper, The Ying and Yang of STAT3 in human disease. J. Clin. Immunol. 35, 615-623 (2015).
60. M. C. Pils, F. Pisano, N. Fasnacht, J.-M. Heinrich, L. Groebe, A. Schippers, B. Rozell, R. S. Jack, W. Müller, Monocytes/macrophages and/or neutrophils are the target of IL-10 in the LPS endotoxemia model. Eur. J. Immunol. 40, 443-448 (2010).
61. L. Madisen, T. A. Zwingman, S. M. Sunkin, S. W. Oh, H. A. Zariwala, H. Gu, L. L. Ng, R. D. Palmiter, M. J. Hawrylycz, A. R. Jones, E. S. Lein, H. Zeng, A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133-140 (2010).
62. D. A. Jaitin, E. Kenigsberg, H. Keren-Shaul, N. Elefant, F. Paul, I. Zaretsky, A. Mildner, N. Cohen, S. Jung, A. Tanay, I. Amit, Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343, 776-779 (2014).
63. S. Heinz, C. Benner, N. Spann, E. Bertolino, Y. C. Lin, P. Laslo, J. X. Cheng, C. Murre, H. Singh, C. K. Glass, Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576-589 (2010).