IL-1β promotes Th17 differentiation by inducing alternative splicing of FOXP3

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Mailer, Reiner K W ^a   Joly, Anne Laure ^a   Liu, Sang ^a   Elias, Szabolcs ^a   Tegner, Jesper ^a   Andersson, John ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; INTERLEUKIN 17; INTERLEUKIN 1BETA; ISOPROTEIN; MESSENGER RNA;

ALTERNATIVE RNA SPLICING; CELL CULTURE; CELL DIFFERENTIATION; CROHN DISEASE; CYTOLOGY; GENETICS; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; PATHOLOGY; PROMOTER REGION; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY T LYMPHOCYTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TH17 CELL; WESTERN BLOTTING;

ALTERNATIVE SPLICING; BLOTTING, WESTERN; CELL DIFFERENTIATION; CELLS, CULTURED; CROHN DISEASE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNE TOLERANCE; INTERLEUKIN-17; INTERLEUKIN-1BETA; LYMPHOCYTE ACTIVATION; PROMOTER REGIONS, GENETIC; PROTEIN ISOFORMS; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; T-LYMPHOCYTES, REGULATORY; TH17 CELLS;

EID: 84943279509     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep14674     Document Type: Article

References (48)

1. Josefowicz, S. Z., Lu, L. F., Rudensky, A. Y. Regulatory t cells: Mechanisms of differentiation and function. Annu. Rev. Immunol. 30, 531-564 (2012).
2. Fontenot, J. D., Gavin, M. A., Rudensky, A. Y. Foxp3 programs the development and function of cd4+ cd25+ regulatory t cells. Nat. Immunol. 4, 330-336 (2003).
3. Hori, S., Nomura, T., Sakaguchi, S. Control of regulatory t cell development by the transcription factor foxp3. Science. 299, 1057-1061 (2003).
4. Khattri, R., Cox, T., Yasayko, S. A., Ramsdell, F. An essential role for scurfin in cd4+ cd25+ t regulatory cells. Nat. Immunol. 4, 337-342 (2003).
5. Brunkow, M. E. et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 27, 68-73 (2001).
6. Bennett, C. L. et al. The immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome (ipex) is caused by mutations of foxp3. Nat. Genet. 27, 20-21 (2001).
7. Wildin, R. S. et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27, 18-20 (2001).
8. Taams, L. S. et al. Regulatory t cells in human disease and their potential for therapeutic manipulation. Immunology 118, 1-9 (2006).
9. Chae, W. J., Henegariu, O., Lee, S. K., Bothwell, A. L. The mutant leucine-zipper domain impairs both dimerization and suppressive function of foxp3 in t cells. P. Natl. Acad. Sci. USA. 103, 9631-9636 (2006).
10. Bettelli, E., Dastrange, M., Oukka, M. Foxp3 interacts with nuclear factor of activated t cells and nf-kappa b to repress cytokine gene expression and effector functions of t helper cells. P. Natl. Acad. Sci. USA. 102, 5138-5143 (2005).
11. Lopes, J. E. et al. Analysis of foxp3 reveals multiple domains required for its function as a transcriptional repressor. J. Immunol. 177, 3133-3142 (2006).
12. Wu, Y. et al. Foxp3 controls regulatory t cell function through cooperation with nfat. Cell. 126, 375-387 (2006).
13. Deng, G. et al. Molecular and biological role of the foxp3 n-terminal domain in immune regulation by t regulatory/suppressor cells. Exp. Mol. Pathol. 93, 334-338 (2012).
14. Li, B. et al. Foxp3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human xlaad/ipex autoimmune disease. Int. Immunol. 19, 825-835 (2007).
15. Song, X. et al. Structural and biological features of foxp3 dimerization relevant to regulatory t cell function. Cell Rep. 1, 665-675 (2012).
16. Bandukwala, H. S. et al. Structure of a domain-swapped foxp3 dimer on DNA and its function in regulatory t cells. Immunity 34, 479-491 (2011).
17. Aarts-Riemens, T., Emmelot, M. E., Verdonck, L. F., Mutis, T. Forced overexpression of either of the two common human foxp3 isoforms can induce regulatory t cells from cd4(+ )cd25(-) cells. Eur. J. Immunol. 38, 1381-1390 (2008).
18. Allan, S. E. et al. The role of 2 foxp3 isoforms in the generation of human cd4+ tregs. J. Clin Invest. 115, 3276-3284 (2005).
19. Mailer, R. K., Falk, K., Rotzschke, O. Absence of leucine zipper in the natural foxp3delta2delta7 isoform does not affect dimerization but abrogates suppressive capacity. PloS One 4, e6104 (2009).
20. Harbuz, R. et al. Identification of new foxp3 mutations and prenatal diagnosis of ipex syndrome. Prenatal Diag. 30, 1072-1078 (2010).
21. Kole, R., Krainer, A. R., Altman, S. Rna therapeutics: Beyond rna interference and antisense oligonucleotides. Nat. Rev. Drug Discov. 11, 125-140 (2012).
22. Ichiyama, K. et al. Foxp3 inhibits rorgammat-mediated il-17a mrna transcription through direct interaction with rorgammat. J. Biol. Chem. 283, 17003-17008 (2008).
23. Zhou, L. et al. Tgf-beta-induced foxp3 inhibits t(h)17 cell differentiation by antagonizing rorgammat function. Nature 453, 236-240 (2008).
24. Lord, J. D., Valliant-Saunders, K., Hahn, H., Thirlby, R. C., Ziegler, S. F. Paradoxically increased foxp3+ t cells in ibd do not preferentially express the isoform of foxp3 lacking exon 2. Digest. Dis. Sci. 57, 2846-2855 (2012).
25. Fu, X. D., Ares, M. Jr. Context-dependent control of alternative splicing by rna-binding proteins. Nat. Rev. Genet. 15, 689-701 (2014).
26. Pan, Q., Shai, O., Lee, L. J., Frey, B. J., Blencowe, B. J. Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40, 1413-1415 (2008).
27. Martinez, N. M., Lynch, K. W. Control of alternative splicing in immune responses: Many regulators, many predictions, much still to learn. Immunol. Rev. 253, 216-236 (2013).
28. Burns, K. et al. Inhibition of interleukin 1 receptor/toll-like receptor signaling through the alternatively spliced, short form of myd88 is due to its failure to recruit irak-4. J. Exp. Med. 197, 263-268 (2003).
29. De Arras, L., Alper, S. Limiting of the innate immune response by sf3a-dependent control of myd88 alternative mrna splicing. PLoS Genet. 9, e1003855 (2013).
30. Meissner, U., Blum, H., Schnare, M., Rollinghoff, M., Gessner, A. A soluble form of the murine common gamma chain is present at high concentrations in vivo and suppresses cytokine signaling. Blood. 97, 183-191 (2001).
31. Hong, C. et al. Activated t cells secrete an alternatively spliced form of common gamma-chain that inhibits cytokine signaling and exacerbates inflammation. Immunity 40, 910-923 (2014).
32. Geremia, A., Biancheri, P., Allan, P., Corazza, G. R., Di Sabatino, A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun. Rev. 13, 3-10 (2014)
33. Monteleone, I., Sarra, M., Pallone, F., Monteleone, G. Th17-related cytokines in inflammatory bowel diseases: Friends or foes? Cur. Mol. Med. 12, 592-597 (2012).
34. Duerr, R. H. et al. A genome-wide association study identifies il23r as an inflammatory bowel disease gene. Science 314, 1461-1463 (2006).
35. Cargill, M. et al. A large-scale genetic association study confirms il12b and leads to the identification of il23r as psoriasis-risk genes. Am. J. Hum Genet. 80, 273-290 (2007).
36. Wellcome Trust Case Control C, et al. Association scan of 14,500 nonsynonymous snps in four diseases identifies autoimmunity variants. Nat. Genet. 39, 1329-1337 (2007).
37. Barrett, J. C. et al. Genome-wide association defines more than 30 distinct susceptibility loci for crohn's disease. Nat. Genet. 40, 955-962 (2008).
38. Fisher, S. A. et al. Genetic determinants of ulcerative colitis include the ecm1 locus and five loci implicated in crohn's disease. Nat. Genet. 40, 710-712 (2008).
39. Chamouard, P. et al. Diminution of circulating cd4+ cd25 high t cells in naive crohn's disease. Digest. Dis. Sci. 54, 2084-2093 (2009).
40. Maul, J. et al. Peripheral and intestinal regulatory cd4+ cd25(high) t cells in inflammatory bowel disease. Gastroenterology 128, 1868-1878 (2005).
41. Saruta, M. et al. Characterization of foxp3+ cd4+ regulatory t cells in crohn's disease. Clin. Immunol. 125, 281/290 (2007).
42. Eastaff-Leung, N., Mabarrack, N., Barbour, A., Cummins, A., Barry, S. Foxp3+ regulatory t cells, th17 effector cells, and cytokine environment in inflammatory bowel disease. J. Clin. Immunol. 30, 80-89 (2010)
43. Ueno, A. et al. Increased prevalence of circulating novel il-17 secreting foxp3 expressing cd4+ t cells and defective suppressive function of circulating foxp3+ regulatory cells support plasticity between th17 and regulatory t cells in inflammatory bowel disease patients. Inflamm. Bowel Dis. 19, 2522-2534 (2013).
44. Raffin, C. et al. Human memory helios-foxp3+ regulatory t cells (tregs) encompass induced tregs that express aiolos and respond to il-1beta by downregulating their suppressor functions. J. Immunol. 191, 4619-4627 (2013).
45. Deknuydt, F., Bioley, G., Valmori, D., Ayyoub, M. Il-1beta and il-2 convert human treg into t(h)17 cells. Clin. Immunol. 131, 298-307 (2009).
46. Chung, Y. et al. Critical regulation of early th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576-587 (2009).
47. Daperno, M. et al. Development and validation of a new, simplified endoscopic activity score for crohn's disease: The ses-cd. Gastrointest. Endosc. 60, 505-512 (2004).
48. Harvey, R. F., Bradshaw, J. M. A simple index of crohn's-disease activity. Lancet 1, 514 (1980).