Foxp3 lacking exons 2 and 7 is unable to confer suppressive ability to regulatory T cells in vivo

Journal of Autoimmunity

Volumn 63, Issue , 2015, Pages 23-30

  Joly, Anne Laure ^a   Liu, Sang ^a   Dahlberg, Carin I M ^a   Mailer, Reiner K W ^a   Westerberg, Lisa S ^a   Andersson, John ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

B cell lymphopoiesis; FOXP3; Inflammatory disease; IPEX; Isoforms; Scurfy

Indexed keywords

CD3 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; HERMES ANTIGEN; L SELECTIN; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; ISOPROTEIN;

ALTERNATIVE RNA SPLICING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN PRESENTING CELL; ARTICLE; B LYMPHOCYTE; CLINICAL FEATURE; CONTROLLED STUDY; CYTOKINE PRODUCTION; EXON; EXON 2; EXON 7; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATION; LYMPHOPROLIFERATIVE DISEASE; MALE; MOUSE; MULTIPLE ORGAN FAILURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; SPLENOMEGALY; T LYMPHOCYTE ACTIVATION; TRANSLATION INITIATION; ANIMAL; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; TRANSGENIC MOUSE;

ANIMALS; EXONS; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; LYMPHOCYTE ACTIVATION; MICE; MICE, TRANSGENIC; PROTEIN ISOFORMS; T-LYMPHOCYTES, REGULATORY;

EID: 84940894580     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2015.06.009     Document Type: Article

References (39)

1. Josefowicz S.Z., Lu L.F., Rudensky A.Y. Regulatory T cells: mechanisms of differentiation and function. Annu. Rev. Immunol. 2012, 30:531-564.
2. Bennett C.L., Christie J., Ramsdell F., Brunkow M.E., Ferguson P.J., Whitesell L., et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 2001, 27:20-21.
3. Brunkow M.E., Jeffery E.W., Hjerrild K.A., Paeper B., Clark L.B., Yasayko S.A., et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 2001, 27:68-73.
4. Wildin R.S., Ramsdell F., Peake J., Faravelli F., Casanova J.L., Buist N., et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 2001, 27:18-20.
5. Taams L.S., Palmer D.B., Akbar A.N., Robinson D.S., Brown Z., Hawrylowicz C.M. Regulatory T cells in human disease and their potential for therapeutic manipulation. Immunology 2006, 118:1-9.
6. + regulatory T cells. Nat. Immunol. 2003, 4:330-336.
7. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003, 299:1057-1061.
8. + T regulatory cells. Nat. Immunol. 2003, 4:337-342.
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. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:9631-9636.
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. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:5138-5143.
11. Lopes J.E., Torgerson T.R., Schubert L.A., Anover S.D., Ocheltree E.L., Ochs H.D., et al. Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J. Immunol. 2006, 177:3133-3142.
12. Wu Y., Borde M., Heissmeyer V., Feuerer M., Lapan A.D., Stroud J.C., et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 2006, 126:375-387.
13. Deng G., Xiao Y., Zhou Z., Nagai Y., Zhang H., Li B., et al. Molecular and biological role of the FOXP3 N-terminal domain in immune regulation by T regulatory/suppressor cells. Exp. Mol. Pathol. 2012, 93:334-338.
14. Li B., Samanta A., Song X., Iacono K.T., Brennan P., Chatila T.A., 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. 2007, 19:825-835.
15. Song X., Li B., Xiao Y., Chen C., Wang Q., Liu Y., et al. Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell Rep. 2012, 1:665-675.
16. Bandukwala H.S., Wu Y., Feuerer M., Chen Y., Barboza B., Ghosh S., et al. Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells. Immunity 2011, 34:479-491.
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. 2008, 38:1381-1390.
18. + Tregs. J. Clin. Invest. 2005, 115:3276-3284.
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 2009, 4:e6104.
20. Harbuz R., Lespinasse J., Boulet S., Francannet C., Creveaux I., Benkhelifa M., et al. Identification of new FOXP3 mutations and prenatal diagnosis of IPEX syndrome. Prenat. Diagn. 2010, 30:1072-1078.
21. Fujita T., Fujii H. Transcription start sites and usage of the first exon of mouse Foxp3 gene. Mol. Biol. Rep. 2012, 39:9613-9619.
22. + regulatory T cell suppressor function. J. Immunol. 2009, 182:2929-2938.
23. - T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J. Immunol. 1994, 153:3764-3774.
24. Zahorsky-Reeves J.L., Wilkinson J.E. The murine mutation scurfy (sf) results in an antigen-dependent lymphoproliferative disease with altered T cell sensitivity. Eur. J. Immunol. 2001, 31:196-204.
25. + regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur. J. Immunol. 2000, 30:1538-1543.
26. Aschermann S., Lehmann C.H., Mihai S., Schett G., Dudziak D., Nimmerjahn F. B cells are critical for autoimmune pathology in scurfy mice. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:19042-19047.
27. Chang S.E., Guo L., Tian J., Liu Y., Guo Z., Zheng B., et al. Autoimmune bone marrow environment severely inhibits B cell development by inducing extensive cell death and inhibiting proliferation. Autoimmunity 2012, 45:210-217.
28. Leonardo S.M., Josephson J.A., Hartog N.L., Gauld S.B. Altered B cell development and anergy in the absence of Foxp3. J. Immunol. 2010, 185:2147-2156.
29. Riewaldt J., Duber S., Boernert M., Krey M., Dembinski M., Weiss S., et al. Severe developmental B lymphopoietic defects in Foxp3-deficient mice are refractory to adoptive regulatory T cell therapy. Front. Immunol. 2012, 3:141.
30. Hardy R.R., Hayakawa K. B cell development pathways. Annu. Rev. Immunol. 2001, 19:595-621.
31. Hardy R.R., Kincade P.W., Dorshkind K. The protean nature of cells in the B lymphocyte lineage. Immunity 2007, 26:703-714.
32. + immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998, 188:287-296.
33. Sadlack B., Merz H., Schorle H., Schimpl A., Feller A.C., Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 1993, 75:253-261.
34. Zheng Y., Josefowicz S., Chaudhry A., Peng X.P., Forbush K., Rudensky A.Y. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 2010, 463:808-812.
35. + regulatory T cells ensure B lymphopoiesis by inhibiting the granulopoietic activity of effector T cells in mouse bone marrow. Eur. J. Immunol. 2015, 45:167-179.
36. van Loosdregt J., Vercoulen Y., Guichelaar T., Gent Y.Y., Beekman J.M., van Beekum O., et al. Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Blood 2010, 115:965-974.
37. de Zoeten E.F., Lee I., Wang L., Chen C., Ge G., Wells A.D., et al. Foxp3 processing by proprotein convertases and control of regulatory T cell function. J. Biol. Chem. 2009, 284:5709-5716.
38. Elhage R., Cherai M., Levacher B., Darrasse-Jeze G., Baillou C., Zhao X., et al. C-terminal cleavage of human Foxp3 at a proprotein convertase motif abrogates its suppressive function. Scand. J. Immunol. 2015, 81:229-239.
39. + T cells-identification of Foxp3Delta7 in human regulatory T cells. Mol. Immunol. 2010, 48:321-332.