JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease

Immunity

Volumn 36, Issue 4, 2012, Pages 542-550

  O'Shea, John J ^a   Plenge, Robert ^b,c  

^a NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AC 430; CEP 33779; GLPG 0634; INCB 28050; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 7; JANUS KINASE; JANUS KINASE INHIBITOR; LESTAURTINIB; R 348; RUXOLITINIB; STAT PROTEIN; STAT3 PROTEIN; STAT5A PROTEIN; STAT5B PROTEIN; STAT6 PROTEIN; TOFACITINIB; UNCLASSIFIED DRUG; VX 509;

ACUTE GRANULOCYTIC LEUKEMIA; AUTOIMMUNE DISEASE; DRUG EFFICACY; ENTERITIS; EPIGENETICS; GAIN OF FUNCTION MUTATION; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC LINKAGE; GRAFT REJECTION; HUMAN; IMMUNOREGULATION; INNATE IMMUNITY; LYMPHOCYTE DIFFERENTIATION; LYMPHOMA; MACROPHAGE; MEMORY T LYMPHOCYTE; MONOTHERAPY; MYELOFIBROSIS; NONHUMAN; PANCREAS CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POLYCYTHEMIA VERA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PSORIASIS; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SJOEGREN SYNDROME; TH17 CELL; TH2 CELL;

AUTOIMMUNE DISEASES; AUTOIMMUNITY; CYTOKINES; GENE EXPRESSION REGULATION; HUMANS; IMMUNITY, INNATE; INTERFERONS; JANUS KINASES; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS;

EID: 84859972127     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2012.03.014     Document Type: Review

References (110)

1. Alloza I., Otaegui D., de Lapuente A.L., Antigüedad A., Varadé J., Núñez C., Arroyo R., Urcelay E., Fernandez O., Leyva L., et al. ANKRD55 and DHCR7 are novel multiple sclerosis risk loci. Genes Immun. 2011, in press. Published online December 1, 2011.
2. Bowes J., Orozco G., Flynn E., Ho P., Brier R., Marzo-Ortega H., Coates L., McManus R., Ryan A.W., Kane D., et al. Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis. Ann. Rheum. Dis. 2011, 70:1641-1644.
3. Burton P.R., Clayton D.G., Cardon L.R., Craddock N., Deloukas P., Duncanson A., Kwiatkowski D.P., McCarthy M.I., Ouwehand W.H., Samani N.J., et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 2007, 39:1329-1337. Wellcome Trust Case Control Consortium, Australo-Anglo-American Spondylitis Consortium (TASC)Australo-Anglo-American Spondylitis Consortium (TASC), Biologics in RA Genetics and Genomics Study Syndicate (BRAGGS) Steering CommitteeBiologics in RA Genetics and Genomics Study Syndicate (BRAGGS) Steering Committee, Breast Cancer Susceptibility Collaboration (UK)Breast Cancer Susceptibility Collaboration (UK).
4. Butcher B.A., Fox B.A., Rommereim L.M., Kim S.G., Maurer K.J., Yarovinsky F., Herbert D.R., Bzik D.J., Denkers E.Y. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog. 2011, 7:e1002236.
5. Cargill M., Schrodi S.J., Chang M., Garcia V.E., Brandon R., Callis K.P., Matsunami N., Ardlie K.G., Civello D., Catanese J.J., 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. 2007, 80:273-290.
6. Casanova J.-L., Holland S.M., Notarangelo L.D. Inborn errors of human JAKs and STATs. Immunity 2012, 36:515-528. this issue.
7. Changelian P.S., Flanagan M.E., Ball D.J., Kent C.R., Magnuson K.S., Martin W.H., Rizzuti B.J., Sawyer P.S., Perry B.D., Brissette W.H., et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003, 302:875-878.
8. Chaudhry A., Rudra D., Treuting P., Samstein R.M., Liang Y., Kas A., Rudensky A.Y. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 2009, 326:986-991.
9. Chen Z., Laurence A., Kanno Y., Pacher-Zavisin M., Zhu B.M., Tato C., Yoshimura A., Hennighausen L., O'Shea J.J. Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc. Natl. Acad. Sci. USA 2006, 103:8137-8142.
10. Chen H., Sun H., You F., Sun W., Zhou X., Chen L., Yang J., Wang Y., Tang H., Guan Y., et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 2011, 147:436-446.
11. Chen Y., Haines C.J., Gutcher I., Hochweller K., Blumenschein W.M., McClanahan T., Hämmerling G., Li M.O., Cua D.J., McGeachy M.J. Foxp3(+) regulatory T cells promote T helper 17 cell development in vivo through regulation of interleukin-2. Immunity 2011, 34:409-421.
12. Cho J.H., Gregersen P.K. Genomics and the multifactorial nature of human autoimmune disease. N. Engl. J. Med. 2011, 365:1612-1623.
13. Chu X., Pan C.M., Zhao S.X., Liang J., Gao G.Q., Zhang X.M., Yuan G.Y., Li C.G., Xue L.Q., Shen M., et al. A genome-wide association study identifies two new risk loci for Graves' disease. Nat. Genet. 2011, 43:897-901. China Consortium for Genetics of Autoimmune Thyroid Disease.
14. Cui W., Liu Y., Weinstein J.S., Craft J., Kaech S.M. An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 2011, 35:792-805.
15. Darnell J.E., Kerr I.M., Stark G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264:1415-1421.
16. Dawson M.A., Bannister A.J., Göttgens B., Foster S.D., Bartke T., Green A.R., Kouzarides T. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 2009, 461:819-822.
17. Dehghan A., Dupuis J., Barbalic M., Bis J.C., Eiriksdottir G., Lu C., Pellikka N., Wallaschofski H., Kettunen J., Henneman P., et al. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation 2011, 123:731-738.
18. 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 2006, 314:1461-1463.
19. Durant L., Watford W.T., Ramos H.L., Laurence A., Vahedi G., Wei L., Takahashi H., Sun H.W., Kanno Y., Powrie F., O'Shea J.J. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 2010, 32:605-615.
20. El Kasmi K.C., Holst J., Coffre M., Mielke L., de Pauw A., Lhocine N., Smith A.M., Rutschman R., Kaushal D., Shen Y., et al. General nature of the STAT3-activated anti-inflammatory response. J. Immunol. 2006, 177:7880-7888.
21. Elliott P., Chambers J.C., Zhang W., Clarke R., Hopewell J.C., Peden J.F., Erdmann J., Braund P., Engert J.C., Bennett D., et al. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 2009, 302:37-48.
22. Elo L.L., Järvenpää H., Tuomela S., Raghav S., Ahlfors H., Laurila K., Gupta B., Lund R.J., Tahvanainen J., Hawkins R.D., et al. Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming. Immunity 2010, 32:852-862.
23. Esashi E., Wang Y.H., Perng O., Qin X.F., Liu Y.J., Watowich S.S. The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8. Immunity 2008, 28:509-520.
24. Ferreira M.A., Matheson M.C., Duffy D.L., Marks G.B., Hui J., Le Souëf P., Danoy P., Baltic S., Nyholt D.R., Jenkins M., et al. Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet 2011, 378:1006-1014. Australian Asthma Genetics Consortium.
25. Fleischmann R., Cutolo M., Genovese M.C., Lee E.B., Kanik K.S., Sadis S., Connell C.A., Gruben D., Krishnaswami S., Wallenstein G., et al. Phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) or adalimumab monotherapy versus placebo in patients with active rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum. 2012, 64:617-629.
26. Franke A., McGovern D.P., Barrett J.C., Wang K., Radford-Smith G.L., Ahmad T., Lees C.W., Balschun T., Lee J., Roberts R., et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat. Genet. 2010, 42:1118-1125.
27. Fridman J.S., Scherle P.A., Collins R., Burn T.C., Li Y., Li J., Covington M.B., Thomas B., Collier P., Favata M.F., et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J. Immunol. 2010, 184:5298-5307.
28. Ghoreschi K., Laurence A., O'Shea J.J. Selectivity and therapeutic inhibition of kinases: to be or not to be?. Nat. Immunol. 2009, 10:356-360.
29. Ghoreschi K., Jesson M.I., Li X., Lee J.L., Ghosh S., Alsup J.W., Warner J.D., Tanaka M., Steward-Tharp S.M., Gadina M., et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J. Immunol. 2011, 186:4234-4243.
30. Good S.R., Thieu V.T., Mathur A.N., Yu Q., Stritesky G.L., Yeh N., O'Malley J.T., Perumal N.B., Kaplan M.H. Temporal induction pattern of STAT4 target genes defines potential for Th1 lineage-specific programming. J. Immunol. 2009, 183:3839-3847.
31. Goswami R., Jabeen R., Yagi R., Pham D., Zhu J., Goenka S., Kaplan M.H. STAT6-dependent regulation of Th9 development. J. Immunol. 2012, 188:968-975.
32. Gough D.J., Corlett A., Schlessinger K., Wegrzyn J., Larner A.C., Levy D.E. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 2009, 324:1713-1716.
33. Granada M., Wilk J.B., Tuzova M., Strachan D.P., Weidinger S., Albrecht E., Gieger C., Heinrich J., Himes B.E., Hunninghake G.M., et al. A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. J. Allergy Clin. Immunol. 2012, 129:840-845. e21.
34. Hand T.W., Cui W., Jung Y.W., Sefik E., Joshi N.S., Chandele A., Liu Y., Kaech S.M. Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proc. Natl. Acad. Sci. USA 2010, 107:16601-16606.
35. Hingorani A.D., Casas J.P., Kuchenbaecker K.B., Engmann J.E., Shah T., Sofat R., Guo Y., Chung C., Peasey A., Pfister R., et al. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 2012, 379:1214-1224. Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium.
36. Hirschfield G.M., Liu X., Xu C., Lu Y., Xie G., Lu Y., Gu X., Walker E.J., Jing K., Juran B.D., et al. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N. Engl. J. Med. 2009, 360:2544-2555.
37. Jakkula E., Leppä V., Sulonen A.M., Varilo T., Kallio S., Kemppinen A., Purcell S., Koivisto K., Tienari P., Sumelahti M.L., et al. Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene. Am. J. Hum. Genet. 2010, 86:285-291.
38. Johnston R.J., Choi Y.S., Diamond J.A., Yang J.A., Crotty S. STAT5 is a potent negative regulator of TFH cell differentiation. J. Exp. Med. 2012, 209:243-250.
39. Karaman M.W., Herrgard S., Treiber D.K., Gallant P., Atteridge C.E., Campbell B.T., Chan K.W., Ciceri P., Davis M.I., Edeen P.T., et al. A quantitative analysis of kinase inhibitor selectivity. Nat. Biotechnol. 2008, 26:127-132.
40. Kremer J.M., Bloom B.J., Breedveld F.C., Coombs J.H., Fletcher M.P., Gruben D., Krishnaswami S., Burgos-Vargas R., Wilkinson B., Zerbini C.A., Zwillich S.H. The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo. Arthritis Rheum. 2009, 60:1895-1905.
41. Kremer J.M., Cohen S., Wilkinson B.E., Connell C.A., French J.L., Gomez-Reino J., Gruben D., Kanik K.S., Krishnaswami S., Pascual-Ramos V., et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum. 2012, 64:970-981.
42. Laurence A., Tato C.M., Davidson T.S., Kanno Y., Chen Z., Yao Z., Blank R.B., Meylan F., Siegel R., Hennighausen L., et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 2007, 26:371-381.
43. Leonard W.J., O'Shea J.J. Jaks and STATs: biological implications. Annu. Rev. Immunol. 1998, 16:293-322.
44. Li W.X. Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol. 2008, 18:545-551.
45. Liao W., Schones D.E., Oh J., Cui Y., Cui K., Roh T.Y., Zhao K., Leonard W.J. Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression. Nat. Immunol. 2008, 9:1288-1296.
46. Liao W., Lin J.X., Leonard W.J. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr. Opin. Immunol. 2011, 23:598-604.
47. Liao W., Lin J.X., Wang L., Li P., Leonard W.J. Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages. Nat. Immunol. 2011, 12:551-559.
48. Lin T.H., Hegen M., Quadros E., Nickerson-Nutter C.L., Appell K.C., Cole A.G., Shao Y., Tam S., Ohlmeyer M., Wang B., et al. Selective functional inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in mice. Arthritis Rheum. 2010, 62:2283-2293.
49. Lu L.D., Stump K.L., Wallace N.H., Dobrzanski P., Serdikoff C., Gingrich D.E., Dugan B.J., Angeles T.S., Albom M.S., Mason J.L., et al. Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2. J. Immunol. 2011, 187:3840-3853.
50. Malin S., McManus S., Cobaleda C., Novatchkova M., Delogu A., Bouillet P., Strasser A., Busslinger M. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat. Immunol. 2010, 11:171-179.
51. Mandal M., Powers S.E., Maienschein-Cline M., Bartom E.T., Hamel K.M., Kee B.L., Dinner A.R., Clark M.R. Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2. Nat. Immunol. 2011, 12:1212-1220.
52. Mandal P.K., Gao F., Lu Z., Ren Z., Ramesh R., Birtwistle J.S., Kaluarachchi K.K., Chen X., Bast R.C., Liao W.S., McMurray J.S. Potent and selective phosphopeptide mimetic prodrugs targeted to the Src homology 2 (SH2) domain of signal transducer and activator of transcription 3. J. Med. Chem. 2011, 54:3549-3563.
53. Mardis E.R. A decade's perspective on DNA sequencing technology. Nature 2011, 470:198-203.
54. Mells G.F., Floyd J.A., Morley K.I., Cordell H.J., Franklin C.S., Shin S.Y., Heneghan M.A., Neuberger J.M., Donaldson P.T., Day D.B., et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 2011, 43:329-332. UK PBC Consortium, Wellcome Trust Case Control Consortium 3Wellcome Trust Case Control Consortium 3.
55. Melzer D., Perry J.R., Hernandez D., Corsi A.M., Stevens K., Rafferty I., Lauretani F., Murray A., Gibbs J.R., Paolisso G., et al. A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet. 2008, 4:e1000072.
56. Milner J.D., Brenchley J.M., Laurence A., Freeman A.F., Hill B.J., Elias K.M., Kanno Y., Spalding C., Elloumi H.Z., Paulson M.L., et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 2008, 452:773-776.
57. Momozawa Y., Mni M., Nakamura K., Coppieters W., Almer S., Amininejad L., Cleynen I., Colombel J.F., de Rijk P., Dewit O., et al. Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease. Nat. Genet. 2011, 43:43-47.
58. Murray P.J. The JAK-STAT signaling pathway: input and output integration. J. Immunol. 2007, 178:2623-2629.
59. Nair R.P., Duffin K.C., Helms C., Ding J., Stuart P.E., Goldgar D., Gudjonsson J.E., Li Y., Tejasvi T., Feng B.J., et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat. Genet. 2009, 41:199-204. Collaborative Association Study of Psoriasis.
60. Nakayama J., Yamamoto M., Hayashi K., Satoh H., Bundo K., Kubo M., Goitsuka R., Farrar M.A., Kitamura D. BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3. Blood 2009, 113:1483-1492.
61. Nakayamada S., Kanno Y., Takahashi H., Jankovic D., Lu K.T., Johnson T.A., Sun H.W., Vahedi G., Hakim O., Handon R., et al. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 2011, 35:919-931.
62. Nelson E.A., Sharma S.V., Settleman J., Frank D.A. A chemical biology approach to developing STAT inhibitors: molecular strategies for accelerating clinical translation. Oncotarget 2011, 2:518-524.
63. Nguyen K.D., Qiu Y., Cui X., Goh Y.P., Mwangi J., David T., Mukundan L., Brombacher F., Locksley R.M., Chawla A. Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 2011, 480:104-108.
64. Nguyen-Jackson H., Panopoulos A.D., Zhang H., Li H.S., Watowich S.S. STAT3 controls the neutrophil migratory response to CXCR2 ligands by direct activation of G-CSF-induced CXCR2 expression and via modulation of CXCR2 signal transduction. Blood 2010, 115:3354-3363.
65. O'Shea J.J., Murray P.J. Cytokine signaling modules in inflammatory responses. Immunity 2008, 28:477-487.
66. Oestreich K.J., Mohn S.E., Weinmann A.S. Molecular mechanisms that control the expression and activity of Bcl-6 in T(H)1 cells to regulate flexibility with a T(FH)-like gene profile. Nat. Immunol. 2012, 13:405-411.
67. Pandiyan P., Conti H.R., Zheng L., Peterson A.C., Mathern D.R., Hernández-Santos N., Edgerton M., Gaffen S.L., Lenardo M.J. CD4(+)CD25(+)Foxp3(+) regulatory T cells promote Th17 cells in vitro and enhance host resistance in mouse Candida albicans Th17 cell infection model. Immunity 2011, 34:422-434.
68. Panopoulos A.D., Zhang L., Snow J.W., Jones D.M., Smith A.M., El Kasmi K.C., Liu F., Goldsmith M.A., Link D.C., Murray P.J., Watowich S.S. STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils. Blood 2006, 108:3682-3690.
69. Paternoster L., Standl M., Chen C.M., Ramasamy A., Bønnelykke K., Duijts L., Ferreira M.A., Alves A.C., Thyssen J.P., Albrecht E., et al. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Nat. Genet. 2012, 44:187-192. Australian Asthma Genetics Consortium (AAGC), Genetics of Overweight Young Adults (GOYA) ConsortiumGenetics of Overweight Young Adults (GOYA) Consortium, EArly Genetics & Lifecourse Epidemiology (EAGLE) ConsortiumEArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium.
70. Paul W.E. What determines Th2 differentiation, in vitro and in vivo?. Immunol. Cell Biol. 2010, 88:236-239.
71. Plenge R. GWASs and the age of human as the model organism for autoimmune genetic research. Genome Biol. 2010, 11:212.
72. Potla R., Koeck T., Wegrzyn J., Cherukuri S., Shimoda K., Baker D.P., Wolfman J., Planchon S.M., Esposito C., Hoit B., et al. Tyk2 tyrosine kinase expression is required for the maintenance of mitochondrial respiration in primary pro-B lymphocytes. Mol. Cell. Biol. 2006, 26:8562-8571.
73. Radstake T.R., Gorlova O., Rueda B., Martin J.E., Alizadeh B.Z., Palomino-Morales R., Coenen M.J., Vonk M.C., Voskuyl A.E., Schuerwegh A.J., et al. Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus. Nat. Genet. 2010, 42:426-429. Spanish Scleroderma Group.
74. Ramachandran A., Horvath C.M. Paramyxovirus disruption of interferon signal transduction: STATus report. J. Interferon Cytokine Res. 2009, 29:531-537.
75. Remmers E.F., Plenge R.M., Lee A.T., Graham R.R., Hom G., Behrens T.W., de Bakker P.I., Le J.M., Lee H.S., Batliwalla F., et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N. Engl. J. Med. 2007, 357:977-986.
76. Remmers E.F., Cosan F., Kirino Y., Ombrello M.J., Abaci N., Satorius C., Le J.M., Yang B., Korman B.D., Cakiris A., et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease. Nat. Genet. 2010, 42:698-702.
77. Ricardo-Gonzalez R.R., Red Eagle A., Odegaard J.I., Jouihan H., Morel C.R., Heredia J.E., Mukundan L., Wu D., Locksley R.M., Chawla A. IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity. Proc. Natl. Acad. Sci. USA 2010, 107:22617-22622.
78. Rochman Y., Kashyap M., Robinson G.W., Sakamoto K., Gomez-Rodriguez J., Wagner K.U., Leonard W.J. Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling. Proc. Natl. Acad. Sci. USA 2010, 107:19455-19460.
79. Saeij J.P., Coller S., Boyle J.P., Jerome M.E., White M.W., Boothroyd J.C. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 2007, 445:324-327.
80. Sarwar N., Butterworth A.S., Freitag D.F., Gregson J., Willeit P., Gorman D.N., Gao P., Saleheen D., Rendon A., Nelson C.P., et al. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 2012, 379:1205-1213. IL6R Genetics Consortium Emerging Risk Factors Collaboration.
81. Schmitt N., Morita R., Bourdery L., Bentebibel S.E., Zurawski S.M., Banchereau J., Ueno H. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity 2009, 31:158-169.
82. Schulz E.G., Mariani L., Radbruch A., Höfer T. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity 2009, 30:673-683.
83. Sewgobind V.D., Quaedackers M.E., van der Laan L.J., Kraaijeveld R., Korevaar S.S., Chan G., Weimar W., Baan C.C. The Jak inhibitor CP-690,550 preserves the function of CD4CD25FoxP3 regulatory T cells and inhibits effector T cells. Am. J. Transplant. 2010, 10:1785-1795.
84. Shi S., Calhoun H.C., Xia F., Li J., Le L., Li W.X. JAK signaling globally counteracts heterochromatic gene silencing. Nat. Genet. 2006, 38:1071-1076.
85. Siegel A.M., Heimall J., Freeman A.F., Hsu A.P., Brittain E., Brenchley J.M., Douek D.C., Fahle G.H., Cohen J.I., Holland S.M., Milner J.D. A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory. Immunity 2011, 35:806-818.
86. Siracusa M.C., Saenz S.A., Hill D.A., Kim B.S., Headley M.B., Doering T.A., Wherry E.J., Jessup H.K., Siegel L.A., Kambayashi T., et al. TSLP promotes interleukin-3-independent basophil haematopoiesis and type 2 inflammation. Nature 2011, 477:229-233.
87. Sonnenberg G.F., Fouser L.A., Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat. Immunol. 2011, 12:383-390.
88. Stahl E.A., Raychaudhuri S., Remmers E.F., Xie G., Eyre S., Thomson B.P., Li Y., Kurreeman F.A., Zhernakova A., Hinks A., et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat. Genet. 2010, 42:508-514. BIRAC Consortium, YEAR ConsortiumYEAR Consortium.
89. Stark G.R., Darnell J.E. The JAK-STAT pathway at twenty. Immunity 2012, 36:503-514. this issue.
90. Stritesky G.L., Muthukrishnan R., Sehra S., Goswami R., Pham D., Travers J., Nguyen E.T., Levy D.E., Kaplan M.H. The transcription factor STAT3 is required for T helper 2 cell development. Immunity 2011, 34:39-49.
91. Stump K.L., Lu L.D., Dobrzanski P., Serdikoff C., Gingrich D.E., Dugan B.J., Angeles T.S., Albom M.S., Ator M.A., Dorsey B.D., et al. A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis. Arthritis Res. Ther. 2011, 13:R68.
92. Szanto A., Balint B.L., Nagy Z.S., Barta E., Dezso B., Pap A., Szeles L., Poliska S., Oros M., Evans R.M., et al. STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells. Immunity 2010, 33:699-712.
93. Tanaka Y., Suzuki M., Nakamura H., Toyoizumi S., Zwillich S.H. Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Care Res (Hoboken) 2011, 63:1150-1158. Tofacitinib Study Investigators.
94. Timofeeva O.A., Gaponenko V., Lockett S.J., Tarasov S.G., Jiang S., Michejda C.J., Perantoni A.O., Tarasova N.I. Rationally designed inhibitors identify STAT3 N-domain as a promising anticancer drug target. ACS Chem. Biol. 2007, 2:799-809.
95. Tripathi P., Kurtulus S., Wojciechowski S., Sholl A., Hoebe K., Morris S.C., Finkelman F.D., Grimes H.L., Hildeman D.A. STAT5 is critical to maintain effector CD8+ T cell responses. J. Immunol. 2010, 185:2116-2124.
96. Trynka G., Hunt K.A., Bockett N.A., Romanos J., Mistry V., Szperl A., Bakker S.F., Bardella M.T., Bhaw-Rosun L., Castillejo G., et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 2011, 43:1193-1201. Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), PreventCD Study GroupPreventCD Study Group, Wellcome Trust Case Control Consortium (WTCCC)Wellcome Trust Case Control Consortium (WTCCC).
97. van Panhuys N., Tang S.C., Prout M., Camberis M., Scarlett D., Roberts J., Hu-Li J., Paul W.E., Le Gros G. In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation. Proc. Natl. Acad. Sci. USA 2008, 105:12423-12428.
98. van Panhuys N., Prout M., Forbes E., Min B., Paul W.E., Le Gros G. Basophils are the major producers of IL-4 during primary helminth infection. J. Immunol. 2011, 186:2719-2728.
99. Wang W.B., Levy D.E., Lee C.K. STAT3 negatively regulates type I IFN-mediated antiviral response. J. Immunol. 2011, 187:2578-2585.
100. Wegrzyn J., Potla R., Chwae Y.J., Sepuri N.B., Zhang Q., Koeck T., Derecka M., Szczepanek K., Szelag M., Gornicka A., et al. Function of mitochondrial Stat3 in cellular respiration. Science 2009, 323:793-797.
101. Wei L., Vahedi G., Sun H.W., Watford W.T., Takatori H., Ramos H.L., Takahashi H., Liang J., Gutierrez-Cruz G., Zang C., et al. Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity 2010, 32:840-851.
102. Yang X.P., Ghoreschi K., Steward-Tharp S.M., Rodriguez-Canales J., Zhu J., Grainger J.R., Hirahara K., Sun H.W., Wei L., Vahedi G., et al. Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat. Immunol. 2011, 12:247-254.
103. Yao Z., Cui Y., Watford W.T., Bream J.H., Yamaoka K., Hissong B.D., Li D., Durum S.K., Jiang Q., Bhandoola A., et al. Stat5a/b are essential for normal lymphoid development and differentiation. Proc. Natl. Acad. Sci. USA 2006, 103:1000-1005.
104. Yao Z., Kanno Y., Kerenyi M., Stephens G., Durant L., Watford W.T., Laurence A., Robinson G.W., Shevach E.M., Moriggl R., et al. Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 2007, 109:4368-4375.
105. Yue P., Turkson J. Targeting STAT3 in cancer: how successful are we?. Expert Opin. Investig. Drugs 2009, 18:45-56.
106. Zhang H., Nguyen-Jackson H., Panopoulos A.D., Li H.S., Murray P.J., Watowich S.S. STAT3 controls myeloid progenitor growth during emergency granulopoiesis. Blood 2010, 116:2462-2471.
107. Zhang X., Yue P., Fletcher S., Zhao W., Gunning P.T., Turkson J. A novel small-molecule disrupts Stat3 SH2 domain-phosphotyrosine interactions and Stat3-dependent tumor processes. Biochem. Pharmacol. 2010, 79:1398-1409.
108. Zhao W., Jaganathan S., Turkson J. A cell-permeable Stat3 SH2 domain mimetic inhibits Stat3 activation and induces antitumor cell effects in vitro. J. Biol. Chem. 2010, 285:35855-35865.
109. Zhernakova A., Stahl E.A., Trynka G., Raychaudhuri S., Festen E.A., Franke L., Westra H.J., Fehrmann R.S., Kurreeman F.A., Thomson B., et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 2011, 7:e1002004.
110. Zorn E., Nelson E.A., Mohseni M., Porcheray F., Kim H., Litsa D., Bellucci R., Raderschall E., Canning C., Soiffer R.J., et al. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 2006, 108:1571-1579.