IL-15 positively regulates IL-21 production in celiac disease mucosa

Mucosal Immunology

Volumn 6, Issue 2, 2013, Pages 244-255

  Sarra, M ^a   Cupi, M L ^a   Monteleone, I ^a   Franze E ^a   Ronchetti, G ^a   Di Sabatino, A ^b   Gentileschi, P ^a   Franceschilli, L ^a   Sileri, P ^a   Sica, G ^a   Del Vecchio Blanco, G ^a   Cretella, M ^a   Paoluzi, O A ^a   Corazza, G R ^b   Pallone, F ^a   Monteleone, G ^a  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; CHEMOKINE RECEPTOR CXCR5; GAMMA INTERFERON; INTERLEUKIN 15; INTERLEUKIN 21; PROTEIN KINASE B; STAT3 PROTEIN;

ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELIAC DISEASE; CELL ISOLATION; CELLULAR DISTRIBUTION; CONTROLLED STUDY; CYTOKINE PRODUCTION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FLOW CYTOMETRY; GAMMA DELTA T LYMPHOCYTE; HUMAN; HUMAN CELL; HUMAN TISSUE; INTRACELLULAR SIGNALING; INTRAEPITHELIAL LYMPHOCYTE; LAMINA PROPRIA LYMPHOCYTE; LYMPHOCYTE; MAJOR CLINICAL STUDY; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; SINGLE CELL ANALYSIS; TH17 CELL;

EID: 84874080477     PISSN: 19330219     EISSN: 19353456     Source Type: Journal    
DOI: 10.1038/mi.2012.65     Document Type: Article

References (49)

1. Green, P. H. & Cellier, C. Celiac disease. N. Engl. J. Med. 357, 1731-1743 (2007).
2. Jabri, B. & Sollid, L. M. Tissue-mediated control of immunopathology in coeliac disease. Nat. Rev. Immunol. 9, 858-870 (2009).
3. Maiuri, L. et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 362, 30-37 (2003).
4. Mention, J. J. et al. Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease. Gastroenterology 125, 730-745 (2003).
5. Maiuri, L. et al. Interleukin 15 mediates epithelial changes in celiac disease. Gastroenterology 119, 996-1006 (2000).
6. Meresse, B. et al. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity 21, 357-366 (2004).
7. De Nitto, D., Monteleone, I., Franze, E., Pallone, F. & Monteleone, G. Involvement of interleukin-15 and interleukin-21, two gamma-chainrelated cytokines, in celiac disease. World J. Gastroenterol. 15, 4609-4614 (2009).
8. Di Sabatino, A. et al. Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 55, 469-477 (2006).
9. Benahmed, M. et al. Inhibition of TGF-beta signaling by IL-15: a new role for IL-15 in the loss of immune homeostasis in celiac disease. Gastroenterology 132, 994-1008 (2007).
10. Nilsen, E. M. et al. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology 115, 551-563 (1998).
11. Monteleone, I. et al. Characterization of IL-17A-producing cells in celiac disease mucosa. J. Immunol. 184, 2211-2218 (2010).
12. Fina, D. et al. Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease. Gut 57, 887-892 (2008).
13. Bodd, M. et al. HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal. Immunol. 3, 594-601 (2010).
14. Strengell, M., Sareneva, T., Foster, D., Julkunen, I. & Matikainen, S. IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. J. Immunol. 169, 3600-3605 (2002).
15. Korn, T. et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448, 484-487 (2007).
16. Monteleone, G. et al. Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21. Gut 55, 1774-1780 (2006).
17. Caruso, R. et al. A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells. Gastroenterology 132, 166-175 (2007).
18. Peluso, I. et al. IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J. Immunol. 178, 732-739 (2007).
19. van Heel, D. A. et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat. Genet. 39, 827-829 (2007).
20. Monteleone, G., Pallone, F. & Macdonald, T. T. Interleukin-21: a critical regulator of the balance between effector and regulatory T-cell responses. Trends Immunol. 29, 290-294 (2008).
21. Halstensen, T. S., Scott, H. & Brandtzaeg, P. Intraepithelial T cells of the TcR gamma/delta+ CD8 - and V delta 1/J delta 1+ phenotypes are increased in coeliac disease. Scand. J. Immunol. 30, 665-672 (1989).
22. Rust, C. et al. Phenotypical and functional characterization of small intestinal TcR gamma delta + T cells in coeliac disease. Scand. J. Immunol. 35, 459-468 (1992).
23. Crotty, S. Follicular helper CD4 T cells (T(FH)). Annu. Rev. Immunol. 29, 621-663 (2011).
24. Bryant, V. L. et al. Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J. Immunol. 179, 8180-8190 (2007).
25. Vinuesa, C. G. et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435, 452-458 (2005).
26. Linterman, M. A. et al. Follicular helper T cells are required for systemic autoimmunity. J. Exp. Med. 206, 561-576 (2009).
27. Breitfeld, D. et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J. Exp. Med. 192, 1545-1552 (2000).
28. Wei, L., Laurence, A., Elias, K. M. & O'Shea, J. J. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J. Biol. Chem. 282, 34605-34610 (2007).
29. Sarra, M. et al. Interferon-gamma-expressing cells are a major source of interleukin-21 in inflammatory bowel diseases. Inflamm. Bowel Dis. 16, 1332-1339 (2010).
30. Szabo, S. J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100, 655-669 (2000).
31. Marzec, M. et al. Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells. Cancer Res. 68, 1083-1091 (2008).
32. Kim, H. R., Hwang, K. A. & Kang, I. Dual roles of IL-15 in maintaining IL-7Ralphalow. J. Immunol. 179, 6734-6740 (2007).
33. De Totero, D. et al. The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways. Blood 111, 517-524 (2008).
34. Zeng, R. et al. The molecular basis of IL-21-mediated proliferation. Blood 109, 4135-4142 (2007).
35. Manning, B. D. & Cantley, L. C. AKT/PKB signaling: navigating downstream. Cell 129, 1261-1274 (2007).
36. Caprioli, F. et al. Autocrine regulation of IL-21 production in human T lymphocytes. J. Immunol. 180, 1800-1807 (2008).
37. Schuppan, D., Junker, Y. & Barisani, D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology 137, 1912-1933 (2009).
38. Kronenberg, M. Antigens recognized by gamma delta T cells. Curr. Opin. Immunol. 6, 64-71 (1994).
39. Bhagat, G. et al. Small intestinal CD8+TCRgammadelta+ NKG2A+ intraepithelial lymphocytes have attributes of regulatory cells in patients with celiac disease. J. Clin. Invest. 118, 281-293 (2008).
40. Sutton, C. E. et al. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity 31, 331-341 (2009).
41. Monteleone, G. et al. Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease. Gastroenterology 128, 687-694 (2005).
42. Caruso, R. et al. IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. J. Immunol. 178, 5957-5965 (2007).
43. King, C., Tangye, S. G. & Mackay, C. R. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu. Rev. Immunol. 26, 741-766 (2008).
44. Malamut, G. et al. IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac diseaseassociated inflammation and lymphomagenesis. J. Clin. Invest. 120, 2131-2143 (2010).
45. Di Cristofano, A. et al. Impaired Fas response and autoimmunity in Pten+/- mice. Science 285, 2122-2125 (1999).
46. Borlado, L. R. et al. Increased phosphoinositide 3-kinase activity induces a lymphoproliferative disorder and contributes to tumor generation in vivo. FASEB J. 14, 895-903 (2000).
47. Barber, D. F. et al. PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat. Med. 11, 933-935 (2005).
48. Barber, D. F. et al. Class IB-phosphatidylinositol 3-kinase (PI3K) deficiency ameliorates IA-PI3K-induced systemic lupus but not T cell invasion. J. Immunol. 176, 589-593 (2006).
49. Wu, T. & Mohan, C. The AKT axis as a therapeutic target in autoimmune diseases. Endocr. Metab. Immune Disord. Drug Targets 9, 145-150 (2009).