リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation

Sakamoto, Yusuke Sasaki, Katsuhiro Omatsu, Mayuki Hamada, Kensuke Nakanishi, Yuki Itatani, Yoshiro Kawada, Kenji Obama, Kazutaka Seno, Hiroshi Iwai, Kazuhiro 京都大学 DOI:10.1002/path.6042

2023.03

概要

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

1. Collaborators GBDIBD. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5: 17-30.

2. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 2006; 3: 390-407.

3. de Souza HS, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol 2016; 13: 13-27.

4. Chang JT. Pathophysiology of Inflammatory Bowel Diseases. N Engl J Med 2020; 383: 2652-2664.

5. Geremia A, Biancheri P, Allan P, et al. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13: 3-10.

6. Schey R, Danzer C, Mattner J. Perturbations of mucosal homeostasis through interactions of intestinal microbes with myeloid cells. Immunobiology 2015; 220: 227-235.

7. Baillie JK, Arner E, Daub C, et al. Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease. PLoS Genet 2017; 13: e1006641.

8. Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 2008; 8: 411-420.

9. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809.

10. Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 2014; 14: 141-153.

11. Nenci A, Becker C, Wullaert A, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 2007; 446: 557-561. 12.

12. Welz PS, Wullaert A, Vlantis K, et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 2011; 477: 330-334.

13. Dannappel M, Vlantis K, Kumari S, et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 2014; 513: 90-94.

14. Takahashi N, Vereecke L, Bertrand MJ, et al. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 2014; 513: 95-99.

15. Gunther C, Buchen B, He GW, et al. Caspase-8 controls the gut response to microbial challenges by Tnf-α-dependent and independent pathways. Gut 2015; 64: 601-610.

16. Eftychi C, Schwarzer R, Vlantis K, et al. Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment. Immunity 2019; 51: 367-380 e364.

17. Schwarzer R, Jiao H, Wachsmuth L, et al. FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells. Immunity 2020; 52: 978-993 e976.

18. Nakanishi Y, Reina-Campos M, Nakanishi N, et al. Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKCλ/ι. Cell Rep 2016; 16: 3297-3310.

19. Iwamoto M, Koji T, Makiyama K, et al. Apoptosis of crypt epithelial cells in ulcerative colitis. J Pathol 1996; 180: 152-159.

20. Gunther C, Martini E, Wittkopf N, et al. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature 2011; 477: 335-339.

21. Smith PD, Smythies LE, Shen R, et al. Intestinal macrophages and response to microbial encroachment. Mucosal Immunol 2011; 4: 31-42.

22. Bain CC, Mowat AM. Macrophages in intestinal homeostasis and inflammation. Immunol Rev 2014; 260: 102-117.

23. Bain CC, Schridde A. Origin, Differentiation, and Function of Intestinal

24. Na YR, Stakenborg M, Seok SH, et al. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat Rev Gastroenterol Hepatol 2019; 16: 531-543.

25. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124: 783-801.

26. Friedrich M, Pohin M, Powrie F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity 2019; 50: 992-1006.

27. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol 2014; 14:329-342.

28. Karin M, Clevers H. Reparative inflammation takes charge of tissue regeneration. Nature 2016; 529: 307-315.

29. Kirisako T, Kamei K, Murata S, et al. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J 2006; 25: 4877-4887.

30. Tokunaga F, Sakata S, Saeki Y, et al. Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nat Cell Biol 2009; 11: 123-132.

31. Iwai K, Tokunaga F. Linear polyubiquitination: a new regulator of NF-κB activation. EMBO Rep 2009; 10: 706-713.

32. Ikeda F, Deribe YL, Skanland SS, et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. Nature 2011; 471: 637-641.

33. Greten FR, Eckmann L, Greten TF, et al. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004; 118: 285-296.

34. Atreya I, Atreya R, Neurath MF. NF-κB in inflammatory bowel disease. J Intern Med 2008; 263: 591-596.

35. Pasparakis M. Regulation of tissue homeostasis by NF-κB signalling: implications

36. Liu T, Zhang L, Joo D, et al. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017; 2.

37. Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491: 119-124.

38. Vereecke L, Vieira-Silva S, Billiet T, et al. A20 controls intestinal homeostasis through cell-specific activities. Nat Commun 2014; 5: 5103.

39. Williams JM, Duckworth CA, Watson AJ, et al. A mouse model of pathological small intestinal epithelial cell apoptosis and shedding induced by systemic administration of lipopolysaccharide. Dis Model Mech 2013; 6: 1388-1399.

40. Chassaing B, Aitken JD, Malleshappa M, et al. Dextran sulfate sodium (DSS)- induced colitis in mice. Curr Protoc Immunol 2014; 104: 15 25 11-15 25 14.

41. Sasaki Y, Iwai K. Crucial Role of Linear Ubiquitin Chain Assembly Complex- Mediated Inhibition of Programmed Cell Death in TLR4-Mediated B Cell Responses and B1b Cell Development. J Immunol 2018; 200: 3438-3449.

42. Sasaki Y, Sano S, Nakahara M, et al. Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells. EMBO J 2013; 32: 2463-2476.

43. el Marjou F, Janssen KP, Chang BH, et al. Tissue-specific and inducible Cre- mediated recombination in the gut epithelium. Genesis 2004; 39: 186-193.

44. Clausen BE, Burkhardt C, Reith W, et al. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res 1999; 8: 265-277.

45. Nakatsuji M, Minami M, Seno H, et al. EP4 Receptor-Associated Protein in Macrophages Ameliorates Colitis and Colitis-Associated Tumorigenesis. PLoS Genet 2015; 11: e1005542.

46. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus

47. Peltzer N, Rieser E, Taraborrelli L, et al. HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death. Cell Rep 2014; 9: 153-165.

48. Peltzer N, Darding M, Montinaro A, et al. LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis. Nature 2018; 557: 112-117.

49. Jones LG, Vaida A, Thompson LM, et al. NF-κB2 signalling in enteroids modulates enterocyte responses to secreted factors from bone marrow-derived dendritic cells. Cell Death Dis 2019; 10: 896.

50. Taraborrelli L, Peltzer N, Montinaro A, et al. LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L. Nat Commun 2018; 9: 3910.

51. Tang Y, Joo D, Liu G, et al. Linear ubiquitination of cFLIP induced by LUBAC contributes to TNFα-induced apoptosis. J Biol Chem 2018; 293: 20062-20072.

52. Watson AJ, Hughes KR. TNF-α-induced intestinal epithelial cell shedding: implications for intestinal barrier function. Ann N Y Acad Sci 2012; 1258: 1-8.

53. Eichele DD, Kharbanda KK. Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J Gastroenterol 2017; 23: 6016-6029.

54. Gantke T, Sriskantharajah S, Sadowski M, et al. IκB kinase regulation of the TPL- 2/ERK MAPK pathway. Immunol Rev 2012; 246: 168-182.

55. Webb LV, Ventura S, Ley SC. ABIN-2, of the TPL-2 Signaling Complex, Modulates Mammalian Inflammation. Trends Immunol 2019; 40: 799-808.

56. Oikawa D, Sato Y, Ohtake F, et al. Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses. Commun Biol 2020; 3: 163.

57. Vereecke L, Beyaert R, van Loo G. Enterocyte death and intestinal barrier maintenance in homeostasis and disease. Trends Mol Med 2011; 17: 584-593.

inflammation by inhibiting TNFR1-induced keratinocyte apoptosis. Elife 2014; 3.

59. Rickard JA, Anderton H, Etemadi N, et al. TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice. Elife 2014; 3.

60. Neurath MF. Current and emerging therapeutic targets for IBD. Nat Rev Gastroenterol Hepatol 2017; 14: 269-278.

61. Pott J, Kabat AM, Maloy KJ. Intestinal Epithelial Cell Autophagy Is Required to Protect against TNF-Induced Apoptosis during Chronic Colitis in Mice. Cell Host Microbe 2018; 23: 191-202 e194.

参考文献をもっと見る