Cytokines that regulate autoimmunity

Current Opinion in Immunology

Volumn 20, Issue 6, 2008, Pages 663-668

  Diveu, Caroline ^a   McGeachy, Mandy J ^a   Cua, Daniel J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 6; TRANSFORMING GROWTH FACTOR BETA;

ANTIINFLAMMATORY ACTIVITY; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; DOWN REGULATION; HELPER CELL; HUMAN; IMMUNE RESPONSE; INFLAMMATION; LEISHMANIASIS; MUCOSAL IMMUNITY; NONHUMAN; PATHOGENESIS; PROTEIN FUNCTION; REVIEW; TOXOPLASMA GONDII; TOXOPLASMOSIS;

ANIMALS; AUTOIMMUNITY; CYTOKINES; HUMANS; INTERLEUKIN-10; INTERLEUKIN-12; INTERLEUKIN-17; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, HELPER-INDUCER;

EID: 56349123128     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coi.2008.09.003     Document Type: Review

References (59)

1. Langrish C.L., Chen Y., Blumenschein W.M., Mattson J., Basham B., Sedgwick J.D., McClanahan T., Kastelein R.A., and Cua D.J. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201 (2005) 233-240. This is the first paper to suggest existence of Th17 cells that are involved in organ-specific autoimmunity.
2. Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A., Lafaille J.J., Cua D.J., and Littman D.R. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126 (2006) 1121-1133. This is the first study to describe the transcriptional control of Th17 cells and it validated that IL-17-producing cells are indeed a unique T cell subset.
3. Wilson N.J., Boniface K., Chan J.R., McKenzie B.S., Blumenschein W.M., Mattson J.D., Basham B., Smith K., Chen T., Morel F., et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8 (2007) 950-957
4. Liang S.C., Tan X.Y., Luxenberg D.P., Karim R., Dunussi-Joannopoulos K., Collins M., and Fouser L.A. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203 (2006) 2271-2279. This is the first paper demonstrating IL-22 is a effector cytokine produced by Th17 cells.
5. ••] proposing existence of Th17 cells. It further demonstrated that Th17 cells are not STAT1, STAT4 or STAT6 dependent and that Type 1 and Type 2 cytokines (e.g. IFNg and IL-4) strongly suppress Th17 cell development.
6. •]. It also showed the signaling requirement of Th17 cells and further demonstrated that IL-17-producing cells are capable of inducing organ-specific autoimmunity.
7. Annunziato F., Cosmi L., Santarlasci V., Maggi L., Liotta F., Mazzinghi B., Parente E., Fili L., Ferri S., Frosali F., et al. Phenotypic and functional features of human Th17 cells. J Exp Med 204 (2007) 1849-1861
8. Duerr R.H., Taylor K.D., Brant S.R., Rioux J.D., Silverberg M.S., Daly M.J., Steinhart A.H., Abraham C., Regueiro M., Griffiths A., et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314 (2006) 1461-1463. This is the first study to demonstrate IL-23R is an inflammatory bowel disease susceptibility gene.
9. Capon F., Di Meglio P., Szaub J., Prescott N.J., Dunster C., Baumber L., Timms K., Gutin A., Abkevic V., Burden A.D., et al. Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum Genet 122 (2007) 201-206
10. Krueger G.G., Langley R.G., Leonardi C., Yeilding N., Guzzo C., Wang Y., Dooley L.T., and Lebwohl M. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med 356 (2007) 580-592. This study provides clinical proof that targetting IL-12/IL-23 is effective for treatment of a skin immune disorder.
11. Tato C.M., and Cua D.J. SnapShot: cytokines I. Cell 132 (2008) 324 324, e321. This SnapShot table shows the relationship and function of cytokines.
12. Tato C.M., and Cua D.J. SnapShot: cytokines II. Cell 132 (2008) 500
13. Veldhoen M., Hocking R.J., Atkins C.J., Locksley R.M., and Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24 (2006) 179-189. This is the first paper demonstrating that TGFβ plus IL-6 promotes differentiation of Th17 cells.
14. Bettelli E., Carrier Y., Gao W., Korn T., Strom T.B., Oukka M., Weiner H.L., and Kuchroo V.K. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441 (2006) 235-238. This paper highlights the relationship between TGFβ-dependent Foxp3+ regulatory T cells and IL-17-producing cells.
15. Korn T., Bettelli E., Gao W., Awasthi A., Jager A., Strom T.B., Oukka M., and Kuchroo V.K. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448 (2007) 484-487
16. Mangan P.R., Harrington L.E., O'Quinn D.B., Helms W.S., Bullard D.C., Elson C.O., Hatton R.D., Wahl S.M., Schoeb T.R., and Weaver C.T. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441 (2006) 231-234. This is the first paper suggesting IL-23 activation of TGFβ-dependent Th17 cells is necessary for host defense against mucosal pathogens.
17. Nurieva R., Yang X.O., Martinez G., Zhang Y., Panopoulos A.D., Ma L., Schluns K., Tian Q., Watowich S.S., Jetten A.M., et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448 (2007) 480-483
18. Acosta-Rodriguez E.V., Napolitani G., Lanzavecchia A., and Sallusto F. Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8 (2007) 942-949
19. Chen Z., Tato C.M., Muul L., Laurence A., and O'Shea J.J. Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 56 (2007) 2936-2946
20. van Beelen A.J., Zelinkova Z., Taanman-Kueter E.W., Muller F.J., Hommes D.W., Zaat S.A., Kapsenberg M.L., and de Jong E.C. Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. Immunity 27 (2007) 660-669
21. Zhou L., Ivanov I.I., Spolski R., Min R., Shenderov K., Egawa T., Levy D.E., Leonard W.J., and Littman D.R. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8 9 (2007) 967-974
22. McGeachy M.J., Bak-Jensen K.S., Chen Y., Tato C.M., Blumenschein W., McClanahan T., and Cua D.J. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol 8 (2007) 1390-1397. This study shows that TGFβ plus IL-6 stimulation induced a population of IL-17-double producing cells and IL-10-double producing cells, which are not capable of inducing EAE. IL-23 stimulation of TGFβ-IL-6-dependent T cells is required for induction of pathogenic T cells.
23. Bettelli E., Sullivan B., Szabo S.J., Sobel R.A., Glimcher L.H., and Kuchroo V.K. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med 200 (2004) 79-87
24. Becher B., Durell B.G., and Noelle R.J. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest 110 (2002) 493-497
25. Ferber I.A., Brocke S., Taylor-Edwards C., Ridgway W., Dinisco C., Steinman L., Dalton D., and Fathman C.G. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 156 (1996) 5-7
26. Willenborg D.O., Fordham S., Bernard C.C., Cowden W.B., and Ramshaw I.A. IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J Immunol 157 (1996) 3223-3227
27. Zhang G.X., Gran B., Yu S., Li J., Siglienti I., Chen X., Kamoun M., and Rostami A. Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta 2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 170 (2003) 2153-2160
28. Li M.O., and Flavell R.A. Contextual regulation of inflammation: a duet by transforming growth factor-beta and interleukin-10. Immunity 28 (2008) 468-476
29. Fiorentino D.F., Bond M.W., and Mosmann T.R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170 (1989) 2081-2095. This is a classic paper demonstrating cytokine cross-regulation of T cell functions.
30. Kuhn R., Lohler J., Rennick D., Rajewsky K., and Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75 (1993) 263-274
31. Stumhofer J.S., Silver J.S., Laurence A., Porrett P.M., Harris T.H., Turka L.A., Ernst M., Saris C.J., O'Shea J.J., and Hunter C.A. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 8 (2007) 1363-1371. This paper provides evidence that IL-6 and IL-27 induce secretion of IL-10 in Th1, Th2, and Th17.
32. Yang X.O., Nurieva R., Martinez G.J., Kang H.S., Chung Y., Pappu B.P., Shah B., Chang S.H., Schluns K.S., Watowich S.S., et al. Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29 (2008) 44-56
33. Belkaid Y., Piccirillo C.A., Mendez S., Shevach E.M., and Sacks D.L. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420 (2002) 502-507
34. Jankovic D., Kullberg M.C., Feng C.G., Goldszmid R.S., Collazo C.M., Wilson M., Wynn T.A., Kamanaka M., Flavell R.A., and Sher A. Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 204 (2007) 273-283
35. Anderson C.F., Oukka M., Kuchroo V.J., and Sacks D. CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J Exp Med 204 (2007) 285-297
36. Pflanz S., Timans J.C., Cheung J., Rosales R., Kanzler H., Gilbert J., Hibbert L., Churakova T., Travis M., Vaisberg E., et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 16 (2002) 779-790. This paper describes the discovery of IL-27.
37. Pflanz S., Hibbert L., Mattson J., Rosales R., Vaisberg E., Bazan J.F., Phillips J.H., McClanahan T.K., de Waal Malefyt R., and Kastelein R.A. WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27. J Immunol 172 (2004) 2225-2231
38. Niedbala W., Wei X.Q., Cai B., Hueber A.J., Leung B.P., McInnes I.B., and Liew F.Y. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol 37 (2007) 3021-3029
39. Collison L.W., Workman C.J., Kuo T.T., Boyd K., Wang Y., Vignali K.M., Cross R., Sehy D., Blumberg R.S., and Vignali D.A. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450 (2007) 566-569
40. Sprecher C.A., Grant F.J., Baumgartner J.W., Presnell S.R., Schrader S.K., Yamagiwa T., Whitmore T.E., O'Hara P.J., and Foster D.F. Cloning and characterization of a novel class I cytokine receptor. Biochem Biophys Res Commun 246 (1998) 82-90
41. Chen Q., Ghilardi N., Wang H., Baker T., Xie M.H., Gurney A., Grewal I.S., and de Sauvage F.J. Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407 (2000) 916-920
42. Yoshida H., Hamano S., Senaldi G., Covey T., Faggioni R., Mu S., Xia M., Wakeham A.C., Nishina H., Potter J., et al. WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection. Immunity 15 (2001) 569-578
43. Hamano S., Himeno K., Miyazaki Y., Ishii K., Yamanaka A., Takeda A., Zhang M., Hisaeda H., Mak T.W., Yoshimura A., et al. WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production. Immunity 19 (2003) 657-667
44. Villarino A., Hibbert L., Lieberman L., Wilson E., Mak T., Yoshida H., Kastelein R.A., Saris C., and Hunter C.A. The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity 19 (2003) 645-655
45. Rosas L.E., Satoskar A.A., Roth K.M., Keiser T.L., Barbi J., Hunter C., de Sauvage F.J., and Satoskar A.R. Interleukin-27R (WSX-1/T-cell cytokine receptor) gene-deficient mice display enhanced resistance to Leishmania donovani infection but develop severe liver immunopathology. Am J Pathol 168 (2006) 158-169
46. Fitzgerald D.C., Ciric B., Touil T., Harle H., Grammatikopolou J., Das Sarma J., Gran B., Zhang G.X., and Rostami A. Suppressive effect of IL-27 on encephalitogenic Th17 cells and the effector phase of experimental autoimmune encephalomyelitis. J Immunol 179 (2007) 3268-3275
47. Sonobe Y., Yawata I., Kawanokuchi J., Takeuchi H., Mizuno T., and Suzumura A. Production of IL-27 and other IL-12 family cytokines by microglia and their subpopulations. Brain Res 1040 (2005) 202-207
48. Li J., Gran B., Zhang G.X., Rostami A., and Kamoun M. IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS during experimental autoimmune encephalomyelitis. J Neurol Sci 232 (2005) 3-9
49. Fitzgerald D.C., Zhang G.X., El-Behi M., Fonseca-Kelly Z., Li H., Yu S., Saris C.J., Gran B., Ciric B., and Rostami A. Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells. Nat Immunol 8 (2007) 1372-1379
50. Amadi-Obi A., Yu C.R., Liu X., Mahdi R.M., Clarke G.L., Nussenblatt R.B., Gery I., Lee Y.S., and Egwuagu C.E. TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13 (2007) 711-718
51. Awasthi A., Carrier Y., Peron J.P., Bettelli E., Kamanaka M., Flavell R.A., Kuchroo V.K., Oukka M., and Weiner H.L. A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8 (2007) 1380-1389
52. -/- mice develop severe neuro-inflammation characterized by a pathogenic CD4 T cell population. IL-27 inhibits the generation of Th17 cells in the presence of TGFβ and IL-6 in a STAT1-dependent manner.
53. -/- mice are more susceptible to EAE and generate more IL-17-producing cells.
54. Chen Z., Laurence A., Kanno Y., Pacher-Zavisin M., Zhu B.M., Tato C., Yoshimura A., Hennighausen L., and O'Shea J.J. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A 103 (2006) 8137-8142
55. Mathur A.N., Chang H.C., Zisoulis D.G., Stritesky G.L., Yu Q., O'Malley J.T., Kapur R., Levy D.E., Kansas G.S., and Kaplan M.H. Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178 (2007) 4901-4907
56. Yoshimura T., Takeda A., Hamano S., Miyazaki Y., Kinjyo I., Ishibashi T., Yoshimura A., and Yoshida H. Two-sided roles of IL-27: induction of Th1 differentiation on naive CD4+ T cells versus suppression of proinflammatory cytokine production including IL-23-induced IL-17 on activated CD4+ T cells partially through STAT3-dependent mechanism. J Immunol 177 (2006) 5377-5385
57. Neufert C., Becker C., Wirtz S., Fantini M.C., Weigmann B., Galle P.R., and Neurath M.F. IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1. Eur J Immunol 37 (2007) 1809-1816
58. Huber M., Steinwald V., Guralnik A., Brustle A., Kleemann P., Rosenplanter C., Decker T., and Lohoff M. IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 20 (2008) 223-234
59. Villarino A.V., Larkin III J., Saris C.J., Caton A.J., Lucas S., Wong T., de Sauvage F.J., and Hunter C.A. Positive and negative regulation of the IL-27 receptor during lymphoid cell activation. J Immunol 174 (2005) 7684-7691