STAT4: A critical regulator of inflammation in vivo

Immunologic Research

Volumn 31, Issue 3, 2005, Pages 231-241

  Kaplan, Mark H ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Disease models; Inflammation; Interferon ; Interleukin 12; Pathogenesis; Signal transducer and activator of transcription 4

Indexed keywords

ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 12 RECEPTOR; INTERLEUKIN 12 RECEPTOR BETA2; JANUS KINASE 2; PROTEIN TYROSINE KINASE; STAT4 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; AUTOIMMUNE DISEASE; B LYMPHOCYTE ACTIVATION; BACTERIAL INFECTION; CELL PROLIFERATION; CONTROLLED STUDY; DENDRITIC CELL; HEMATOPOIESIS; IMMUNE MEDIATED INJURY; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOLOGICAL TOLERANCE; INFLAMMATION; MACROPHAGE ACTIVATION; MEDIATOR RELEASE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTOZOAL INFECTION; REVIEW; T LYMPHOCYTE ACTIVATION; TUMOR IMMUNITY; VIRUS INFECTION;

ANIMALS; AUTOIMMUNE DISEASES; BACTERIAL INFECTIONS; CYTOKINES; HEMATOPOIESIS; HISTOCOMPATIBILITY ANTIGENS CLASS II; HYPERSENSITIVITY; IMMUNE TOLERANCE; INFLAMMATION; MICE; MICE, KNOCKOUT; NEOPLASMS; PARASITIC DISEASES; SIGNAL TRANSDUCTION; STAT4 TRANSCRIPTION FACTOR; TRANSPLANTATION IMMUNOLOGY; VIRUS DISEASES;

EID: 18244392419     PISSN: 0257277X     EISSN: None     Source Type: Journal    
DOI: 10.1385/IR:31:3:231     Document Type: Review

References (65)

1. Leonard WJ, O'Shea JJ: Jaks and STATs: biological implications. Annu Rev Immunol 1998;16:293-322.
2. O'Shea JJ, Gadina M, Schreiber RD: Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 2002;109(Suppl):S121-S131.
3. Trinchieri G: Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003;3:133-146.
4. Presky DH, Yang H, Minetti LJ, Chua AO, Nabavi N, Wu C-Y, Gately MK, Gubler U: A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl Acad Sci USA 1996;93:14,002-14,007.
5. Zou J, Presky DH, Wu C-Y, Gubler U: Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits β1 and β2 and JAK kinases. J Biol Chem 1997;272:6073-6077.
6. Yamamoto K, Quelle FW, Thierfelder WE, Kreider BL, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O, Ihie JN: Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation. Mol Cell Biol 1994;14:4342-4349.
7. Zhong Z, Wen Z, Darnell JE Jr: Stat3 and Stat4: members of the family of signal transducers and activators of transcription. Proc Natl Acad Sci USA 1994;91: 4806-4810.
8. Hoey T, Zhang S, Schmidt N, Yu Q, Ramchandani S, Xu X, Naeger LK, Sun YL, Kaplan MH: Distinct requirements for the naturally occurring splice forms Stat4α and Stat4β in IL-12 responses. EMBO J 2003;22:4237-4248.
9. Kaplan MH, Sun Y-L, Hoey T, Grusby MJ: Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 1996;382:174-177.
10. Lawless VA, Zhang S, Ozes ON, Bruns HA, Oldham I, Hoey T, Grusby MJ, Kaplan MH: Stat4 regulates multiple components of IFN-γ-inducing signaling pathways. J Immunol 2000;165:6803-6808.
11. Thierfelder WE, van Deursen JM, Yamamoto K, et al: Requirement for Stat4 in interleukin-12 mediated responses of natural killer and T cells. Nature 1996; 382:171-174.
12. Ouyang W, Jacobson NG, Bhattacharya D, Gorham JD, Fenoglio D, Sha WC, Murphy TL, Murphy KM: The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway. Proc Natl Acad Sci USA 1999;96:3888-3893.
13. White SJ, Underhill GH, Kaplan MH, Kansas GS: Cutting edge: differential requirements for Stat4 in expression of glycosyltransferases responsible for selectin ligand formation in Th1 cells. J Immunol 2001;167: 628-631.
14. Lim YC, Xie H, Come CE, Alexander SI, Grusby MJ, Lichtman AH, Luscinskas FW: IL-12, STAT4-dependent up-regulation of CD4(+) T cell core 2 beta-1,6-n-acetyl-glucosaminyltransferase, an enzyme essential for biosynthesis of P-selectin ligands. J Immunol 2001; 167:4447-4484.
15. Kaplan MH, Wurster AL, Grusby MJ: A Stat4-independent pathway for the development of Th1 cells. J Exp Med 1998;188:1191-1196.
16. Kishimoto K, Dong VM, Issazadeh S, et al: The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo. J Clin Invest 2000;106:63-72.
17. Shi HN, Grusby MJ, Nagler-Anderson C: Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. J Immunol 1999;162:5143-5148.
18. Chang HC, Zhang S, Kaplan MH: Neonatal tolerance in the absence of Stat4- and Stat6-dependent Th cell differentiation. J Immunol 2002;169:4124-4128.
19. Chitnis T, Salama AD, Grusby MJ, Sayegh MH, Khoury SJ: Defining Th1 and Th2 immune responses in a reciprocal cytokine environment in vivo. J Immunol 2004; 172:4260-4265.
20. Chitnis T, Najafian N, Benou C, Salama AD, Grusby MJ, Sayegh MH, Khoury SJ: Effect of targeted disruption of STAT4 and STAT6 on the induction of experimental autoimmune encephalomyelitis. J Clin Invest 2001;108: 739-747.
21. Finnegan A, Grusby MJ, Kaplan CD, O'Neill SK, Eibel H, Koreny T, Czipri M, Mikecz K, Zhang J: IL-4 and IL-12 regulate proteoglycan-induced arthritis through Stat-dependent mechanisms. J Immunol 2002;169:3345-3352.
22. Simpson SJ, Shah S, Comiskey M, de Jong YP, Wang B, Mizoguchi E, Bhan AK, Terhorst C: T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. J Exp Med 1998;187:1225-1234.
23. Afanasyeva M, Wang Y, Kaya Z, Stafford EA, Dohmen KM, Sadighi Akha AA, Rose NR: Interleukin-12 receptor/STAT4 signaling is required for the development of autoimmune myocarditis in mice by an interferon-gamma-independent pathway. Circulation 2001;104:3145-3151.
24. Yang Z, Chen M, Ellett JD, Fialkow LB, Carter JD, McDuffie M, Nadler JL: Autoimmune diabetes is blocked in Stat4-deficient mice. J Autoimmun 2004; 22:191-200.
25. Holz A, Bot A, Coon B, Wolfe T, Grusby MJ, von Herrath MG: Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence. J Immunol 1999;163: 5374-5382.
26. Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, Dalton D, Fathman CG: Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 1996;156:5-7.
27. Wang W, Ostlie NS, Conti-Fine BM, Milani M: The susceptibility to experimental myasthenia gravis of STAT6-/- and STAT4-/- BALB/c mice suggests a pathogenic role of Th1 cells. J Immunol 2004;172:97-103.
28. Land KJ, Moll JS, Kaplan MH, Seetharamaiah GS: Signal transducer and activator of transcription (Stat)-6-dependent, but not Stat4-dependent, immunity is required for the development of autoimmunity in Graves' hyperthyroidism. Endocrinology 2004;145:3724-3730.
29. Jacob CO, Zang S, Li L, Ciobanu V, Quismorio F, Mizutani A, Satoh M, Koss M: Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice. J Immunol 2003;171: 1564-1571.
30. Singh RR, Saxena V, Zang S, Li L, Finkelman FD, Witte DP, Jacob CO: Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis. J Immunol 2003;170:4818-4825.
31. Tekkanat KK, Maassab H, Berlin AA, Lincoln PM, Evanoff HL, Kaplan MH, Lukacs NW: Role of interleukin-12 and stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection. Am J Pathol 2001;159:631-638.
32. Raman K, Kaplan MH, Hogaboam CM, Berlin A, Lukacs NW: STAT4 signal pathways regulate inflammation and airway physiology changes in allergic airway inflammation locally via alteration of chemokines. J Immunol 2003;170:3859-3865.
33. Zhou P, Szot GL, Quo Z, Kim O, He G, Wang J, Grusby MJ, Newell KA, Thistlethwaite JR, Bluestone JA, Alegre ML: Role of STAT4 and STAT6 signaling in allograft rejection and CTLA4-Ig-mediated tolerance. J Immunol 2000;165:5580-5587.
34. Koglin J, Glysing-Jensen T, Gadiraju S, Russell ME: Attenuated cardiac allograft vasculopathy in mice with targeted deletion of the transcription factor STAT4. Circulation 2000;101:1034-1039.
35. Nikolic B, Lee S, Bronson RT, Grusby MJ, Sykes M: Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets. J Clin Invest 2000;105:1289-1298.
36. Kato A, Graul-Layman A, Edwards MJ, Lentsch AB: Promotion of hepatic ischemia/reperfusion injury by IL-12 is independent of STAT4. Transplantation 2002;73: 1142-1145.
37. Shen XD, Ke B, Zhai Y, Gao F, Anselmo D, Lassman CR, Busuttil RW, Kupiec-Weglinski JW: Stat4 and Stat6 signaling in hepatic ischemia/reperfusion injury in mice: HO-1 dependence of Stat4 disruption-mediated cytoprotection. Hepatology 2003;37:296-303.
38. Yokota N, Burne-Taney M, Racusen L, Rabb H: Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 2003;285:F319-325.
39. Ostrand-Rosenberg S, Grusby MJ, Clements VK: Cutting edge: STAT6-deficient mice have enhanced tumor immunity to primary and metastatic mammary carcinoma. J Immunol 2000;165:6015-6019.
40. Zhang SS, Weite T, Fu XY: Dysfunction of Stat4 leads to accelerated incidence of chemical-induced thymic lymphomas in mice. Exp Mol Pathol 2001;70:231-238.
41. Cai G, Radzanowski T, Villegas EN, Kastelein R, Hunter CA: Identification of STAT4-dependent and independent mechanisms of resistance to Toxoplasma gondii. J Immunol 2000;165:2619-2627.
42. Buxbaum LU, Uzonna JE, Goldschmidt MH, Scott P: Control of New World cutaneous leishmaniasis is IL-12 independent but STAT4 dependent. Eur J Immunol 2002;32:3206-3215.
43. Stamm LM, Satoskar AA, Ghosh SK, David JR, Satoskar AR: STAT-4 mediated IL-12 signaling pathway is critical for the development of protective immunity in cutaneous leishmaniasis. Eur J Immunol 1999;29: 2524-2529.
44. Tarleton RL, Grusby MJ, Zhang L: Increased susceptibility of Stat4-deficient and enhanced resistance in Stat6-deficient mice to infection with Trypanosoma cruzi. J Immunol 2000;165:1520-1525.
45. Rodriguez-Sosa M, Monteforte GM, Satoskar AR: Susceptibility to Leishmania mexicana infection is due to the inability to produce IL-12 rather than lack of IL-12 responsiveness. Immunol Cell Biol 2001;79:320-322.
46. Fukao T, Frucht DM, Yap G, Gadina M, O'Shea JJ, Koyasu S: Inducible expression of Stat4 in dendritic cells and macrophages and its critical role in innate and adaptive immune responses. J Immunol 2001;166:4446-4455.
47. Kaplan MH, Whitfield JR, Boros DL, Grusby MJ: Th2 cells are required for the Schistosoma mansoni egg-induced granulomatous response. J Immunol 1998;160: 1850-1856.
48. Rodriguez-Sosa M, Saavedra R, Tenorio EP, Rosas LE, Satoskar AR, Terrazas LI: A STAT4-dependent Th1 response is required for resistance to the helminth parasite Taenia crassiceps. Infect Immun 2004;72:4552-4560.
49. Broxmeyer HE, Bruns HA, Zhang S, et al: Th1 cells regulate hematopoietic progenitor cell homeostasis by production of Oncostatin M. Immunity 2002;16:815-825.
50. Kaplan MH, Chang HC, Cooper S, Lee Y, Broxmeyer HE: Distinct requirements for Stat4 and Stat6 in hematopoietic progenitor cell responses to growth factors and chemokines. J Hematother Stem Cell Res 2003; 12:401-408.
51. Carter LL, Murphy KM: Lineage-specific requirement for signal transducer and activator of transcription (Stat)4 in interferon γ production from CD4+ versus CD8+ T cells. J Exp Med 1999;189:1355-1360.
52. Nguyen KB, Watford WT, Salomon R, Hofmann SR, Pien GC, Morinobu A, Gadina M, O'Shea JJ, Biron CA: Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science 2002;297:2063-2066.
53. Bot A, Rodrigo E, Wolfe T, Bot S, Von Herrath MG: Infection-triggered regulatory mechanisms override the role of STAT4 in control of the immune response to influenza virus antigens. J Virol 2003;77:5794-5800.
54. Chesler DA, Reiss CS: IL-12, while beneficial, is not essential for the host response to VSV encephalitis. J Neuroimmunol 2002;131:92-97.
55. Matsukawa A, Kaplan MH, Hogaboam CM, Lukacs NW, Kunkel SL: Pivotal role of signal transducer and activator of transcription (Stat)4 and Stat6 in the innate immune response during sepsis. J Exp Med 2001; 193:679-688.
56. Godshall CJ, Lentsch AB, Peyton JC, Scott MJ, Cheadle WG: STAT4 is required for antibacterial defense but enhances mortality during polymicrobial sepsis. Clin Diagn Lab Immunol 2001;8:1044-1048.
57. Lentsch AB, Kato A, Davis B, Wang W, Chao C, Edwards MJ: STAT4 and STAT6 regulate systemic inflammation and protect against lethal endotoxemia. J Clin Invest 2001;108:1475-1482.
58. Kamezaki K, Shimoda K, Numata A, Matsuda T, Nakayama K, Harada M: The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals. Int Immunol 2004;16:1173-1179.
59. Chung DR, Chitnis T, Panzo RJ, Kasper DL, Sayegh MH, Tzianabos AO: CD4+ T cells regulate surgical and postinfectious adhesion formation. J Exp Med 2002;195: 1471-1478.
60. Chung DR, Kasper DL, Panzo RJ, Chitnis T, Grusby MJ, Sayegh MH, Tzianabos AO: CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism. J Immunol 2003;170:1958-1963.
61. Sugawara I, Yamada H, Mizuno S: Relative importance of STAT4 in murine tuberculosis. J Med Microbiol 2003;52:29-34.
62. Toyoda H, Ido M, Hayashi T, et al: Impairment of IL-12-dependent STAT4 nuclear translocation in a patient with recurrent Mycobacterium avium infection. J Immunol 2004;172:3905-3912.
63. Cho SS, Bacon CM, Sudarshan C, Rees RC, Finbloom D, Pine R, O'Shea JJ: Activation of Stat4 by IL-12 and IFN-α: evidence for the involvement of ligand induced tyrosine and serine phosphorylation. J Immunol 1996;157:4781-4789.
64. Oppmann B, Lesley R, Blom B, et al: Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000;13:715-725.
65. Cua DJ, Sherlock J, Chen Y, et al: Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421: 744-748.