IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells

Proceedings of the National Academy of Sciences of the United States of America

Volumn 105, Issue 47, 2008, Pages 18460-18465

  Korn, Thomas ^a   Mitsdoerffer, Meike ^b   Croxford, Andrew L ^c   Awasthi, Amit ^b   Dardalhon, Valérie A ^b   Galileos, George ^b   Vollmar, Patrick ^a   Stritesky, Gretta L ^d   Kaplan, Mark H ^d   Waisman, Ari ^c   Kuchroo, Vijay K ^b   Oukka, Mohamed ^b  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b HARVARD MEDICAL SCHOOL   (United States)

^c JOHANNES GUTENBERG UNIVERSITY   (Germany)

^d INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Experimental autoimmune encephalomyelitis; IL 21; Incomplete Freund's adjuvant; Multiple sclerosis; Tolerance

Indexed keywords

FREUND ADJUVANT; INTERLEUKIN 6; TRANSCRIPTION FACTOR FOXP3;

ALLERGIC ENCEPHALOMYELITIS; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; HELPER CELL; IMMUNITY; IMMUNIZATION; KNOCKOUT MOUSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; WILD TYPE;

ANIMALS; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; FORKHEAD TRANSCRIPTION FACTORS; INTERLEUKIN-6; MICE; MICE, KNOCKOUT; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY;

MUS;

EID: 57449112782     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0809850105     Document Type: Article

References (33)

1. Kim JM, Rasmussen JP, Rudensky AY (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8:191-197.
2. Fontenot JD, et al. (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22:329-341.
3. Knoechel B, Lohr J, Kahn E, Bluestone JA, Abbas AK (2005) Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med 202:1375-1386.
4. Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3:253-257.
5. Kamanaka M, et al. (2006) Expression of interleukin-10 in intestinal lymphocytes detected by an interleukin-10 reporter knockin tiger mouse. Immunity 25:941-952.
6. + regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J Exp Med 204:1757-1764.
7. Bettelli E, et al. (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235-238.
8. Korn T, et al. (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448:484-487.
9. Hirano T, et al. (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73-76.
10. Taga T, et al. (1989) Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58:573-581.
11. Kamimura D, Ishihara K, Hirano T (2003) IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol 149:1-38.
12. Yoshida K, et al. (1996) Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders. Proc Natl Acad Sci USA 93:407-411.
13. Atsumi T, et al. (2002) A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis. J Exp Med 196:979-990.
14. Eugster HP, Frei K, Kopf M, Lassmann H, Fontana A (1998) IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. Eur J Immunol 28:2178-2187.
15. Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA, Jr (1993) Surface expression of α4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 177:57-68.
16. Korn T, et al. (2007) Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13:423-431.
17. Heeger PS, et al. (2000) Revisiting tolerance induced by autoantigen in incomplete Freund's adjuvant. J Immunol 164:5771-5781.
18. Jain R, et al. (2008) Innocuous IFNγ induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production. J Exp Med 205:207-218.
19. Zhou L, et al. (2008) TGF-β-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing ROR-γt function. Nature 453:236-240.
20. Manel N, Unutmaz D, Littman DR (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-β and induction of the nuclear receptor ROR-γt. Nat Immunol 9:641-649.
21. Yang XO, et al. (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282:9358-9363.
22. + T helper cells. Cell 126:1121-1133.
23. Yang XO, et al. (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR-α and ROR-γ. Immunity 28:29-39.
24. Spolski R, Leonard WJ (2008) Interleukin-21: Basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 26:57-79.
25. Yang XO, et al. (2008) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29:44-56.
26. Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI (2008) Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol 180:7097-7101.
27. Serada S, et al. (2008) IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA 105:9041-9046.
28. Marusic S, Tonegawa S (1997) Tolerance induction and autoimmune encephalomyelitis amelioration after administration of myelin basic protein-derived peptide. J Exp Med 186:507-515.
29. Conant SB, Swanborg RH (2004) Autoreactive T cells persist in rats protected against experimental autoimmune encephalomyelitis and can be activated through stimulation of innate immunity. J Immunol 172:5322-5328.
30. Swierkosz JE, Swanborg RH (1977) Immunoregulation of experimental allergic encephalomyelitis: Conditions for induction of suppressor cells and analysis of mechanism. J Immunol 119:1501-1506.
31. Apostolou I, von Boehmer H (2004) In vivo instruction of suppressor commitment in naïve T cells. J Exp Med 199:1401-1408.
32. Betz UA, et al. (1998) Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J Exp Med 188:1955-1965.
33. Reddy J, et al. (2003) Detection of autoreactive myelin proteolipid protein 139-151-specific T cells by using MHC II (IAs) tetramers. J Immunol 170:870-877.