SOCS, inflammation, and autoimmunity

Frontiers in Immunology

Volumn 3, Issue MAR, 2012, Pages

  Yoshimura, Akihiko ^a   Suzuki, Mayu ^a   Sakaguchi, Ryota ^a   Hanada, Toshikatsu ^a   Yasukawa, Hideo ^b  

^a KEIO UNIVERSITY   (Japan)

^b KURUME UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Cytokine; Helper T cell; Immunity; Signal transduction; STAT

Indexed keywords

EID: 84864920746     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00020     Document Type: Review

References (86)

1. Adamson, A. S., Collins, K., Laurence, A., and O'Shea, J. J. (2009). The Current STATus of lymphocyte signaling: new roles for old players. Curr. Opin. Immunol. 21, 161-166.
2. Alexander, W. S., Starr, R., Fenner, J. E., Scott, C. L., Handman, E., Sprigg, N. S., Corbin, J. E., Cornish, A. L., Darwiche, R., Owczarek, C. M., Kay, T. W., Nicola, N. A., Hertzog, P. J., Metcalf, D., and Hilton, D. J. (1999). SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98, 597-608.
3. Bhattacharyya, S., Zhao, Y., Kay, T. W., and Muglia, L. J. (2011). Glucocorticoids target suppressor of cytokine signaling 1 (SOCS1) and type 1 interferons to regulate Tolllike receptor-induced STAT1 activation. Proc. Natl. Acad. Sci. U.S.A. 108, 9554-9559.
4. Bjorbak, C., Lavery, H. J., Bates, S. H., Olson, R. K., Davis, S. M., Flier, J. S., and Myers, M. G. Jr. (2000). SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J. Biol. Chem. 275, 40649-40657.
5. Cacalano, N. A., Sanden, D., and Johnston, J. A. (2001). Tyrosinephosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nat. Cell Biol. 3, 460-465.
6. Cao, W., Yang, Y., Wang, Z., Liu, A., Fang, L., Wu, F., Hong, J., Shi, Y., Leung, S., Dong, C., and Zhang, J. Z. (2011). Leukemia inhibitory factor inhibits T helper 17 cell differentiation and confers treatment effects of neural progenitor cell therapy in autoimmune disease. Immunity 35, 273-284.
7. Carow, B., Ye, X., Gavier-Widen, D., Bhuju, S., Oehlmann, W., Singh, M., Skold, M., Ignatowicz, L., Yoshimura, A., Wigzell, H., and Rottenberg, M. E. (2011). Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis controlinan interferon-gamma (IFN-gamma)dependent manner. J. Biol. Chem. 286, 26873-26887.
8. Chen, Z., Laurence, A., Kanno, Y., Pacher-Zavisin, M., Zhu, B. M., Tato, C., Yoshimura, A., Hennighausen, L., and O'Shea, J. J. (2006). Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc. Natl.Acad. Sci. U.S.A. 103, 8137-8142.
9. Chinen, T., Komai, K., Muto, G., Morita, R., Inoue, N., Yoshida, H., Sekiya, T., Yoshida, R., Nakamura, K., Takayanagi, R., and Yoshimura, A (2011). Prostaglandin E2 and SOCS1 have a role in intestinal immune tolerance. Nat. Commun. 2, 190.
10. Croker,B.A.,Kiu,H.,Pellegrini,M.,Toe, J.,Preston,S.,Metcalf,D.,O'Donnell, J. A., Cengia, L. H., McArthur, K., Nicola, N. A., Alexander, W. S., and Roberts, A. W. (2012). IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3. Immunol. Cell Biol. 90, 124-129.
11. Croker, B. A., Metcalf, D., Robb, L., Wei, W., Mifsud, S., DiRago, L., Cluse, L. A., Sutherland, K. D., Hartley, L., Williams, E., Zhang, J. G., Hilton, D. J.,Nicola,N. A.,Alexander,W. S.,and Roberts, A. W. (2004). SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 20, 153-165.
12. Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., Miyazaki, T., Leonor, N., Taniguchi, T., Fujita, T., Kanakura, Y., Komiya, S., and Yoshimura, A. (1997). A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387, 921-924.
13. Guillem, V., Amat, P., Cervantes, F., Alvarez-Larran, A., Cervera, J., Maffioli, M., Bellosillo, B., Collado, M., Marugan, I., Martinez-Ruiz, F., and Hernández-Boluda, J. C. (2012). Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia. Leuk. Res. 36, 174-181.
14. Haffner, M. C., Jurgeit, A., Berlato, C., Geley, S., Parajuli, N., Yoshimura, A., and Doppler, W. (2008). Interaction and functional interference of glucocorticoid receptor and SOCS1. J. Biol. Chem. 283, 22089-22096.
15. Hanada, T., Kobayashi, T., Chinen, T., Saeki, K., Takaki, H., Koga, K., Minoda, Y., Sanada, T., Yoshioka, T., Mimata, H., Kato, S., and Yoshimura, A. (2006). IFNgammadependent, spontaneous development of colorectal carcinomas in SOCS1-deficient mice. J. Exp. Med. 203, 1391-1397.
16. Hanada, T., Tanaka, K., Matsumura, Y., Yamauchi, M., Nishinakamura, H., Aburatani, H., Mashima, R., Kubo, M., Kobayashi, T., andYoshimura, A. (2005). Induction of hyper Th1 cell-type immune responses by dendritic cells lacking the suppressor of cytokine signaling-1 gene. J. Immunol. 174, 4325-4332.
17. Hanada, T., Yoshida, H., Kato, S., Tanaka, K., Masutani, K., Tsukada, J., Nomura, Y., Mimata, H., Kubo, M., and Yoshimura, A. (2003). Suppressor of cytokine signaling-1 is essential for suppressing dendritic cell activation and systemic autoimmunity. Immunity 19, 437-450.
18. Harada, M., Nakashima, K., Hirota, T., Shimizu, M., Doi, S., Fujita, K., Shirakawa, T., Enomoto, T., Yoshikawa, M., Moriyama, H., Matsumoto, K., Saito, H., Suzuki, Y., Nakamura, Y., and Tamari, M. (2007). Functional polymorphism in the suppressor of cytokine signaling 1 gene associated with adult asthma. Am. J. Respir. Cell Mol. Biol. 36, 491-496.
19. Hashimoto, M., Ayada, T., Kinjyo, I., Hiwatashi, K., Yoshida, H., Okada, Y., Kobayashi, T., and Yoshimura, A. (2009). Silencing of SOCS1 in macrophages suppresses tumor development by enhancing antitumor inflammation. Cancer Sci. 100, 730-736.
20. Hashimoto, M., Hiwatashi, K., Ichiyama, K., Morita, R., Sekiya, T., Kimura, A., Sugiyama, Y., Sibata, T., Kuroda, K., Takahashi, R., and Yoshimura, A. (2011). SOCS1 regulates type I/type II NKT cell balance by regulating IFNgamma signaling. Int. Immunol. 23, 165-176.
21. Hiwatashi, K., Tamiya, T., Hasegawa, E., Fukaya, T., Hashimoto, M., Kakoi, K., Kashiwagi, I., Kimura, A., Inoue, N., Morita, R., Yasukawa, H., and Yoshimura, A. (2011). Suppression of SOCS3 in macrophages prevents cancer metastasis by modifying macrophage phase and MCP2/CCL8 induction. Cancer Lett. 308, 172-180.
22. Horino, J., Fujimoto, M., Terabe, F., Serada, S., Takahashi, T., Soma, Y., Tanaka, K., Chinen, T., Yoshimura, A., Nomura, S., Kawase, I., Hayashi, N., Kishimoto, T., and Naka, T. (2008). Suppressor of cytokine signaling-1 ameliorates dextran sulfate sodium-induced colitis in mice. Int. Immunol. 20, 753-762.
23. Ichiyama, K., Hashimoto, M., Sekiya, T., Nakagawa, R., Wakabayashi, Y., Sugiyama, Y., Komai, K., Saba, I., Moroy, T., andYoshimura,A. (2009). Gfi1 negatively regulates T(h)17 differentiation by inhibiting RORgammat activity. Int. Immunol. 21, 881-889.
24. Ichiyama, K., Sekiya, T., Inoue, N., Tamiya, T., Kashiwagi, I., Kimura, A., Morita, R., Muto, G., Shichita, T., Takahashi, R., and Yoshimura, A. (2011). Transcription factor Smadindependent T helper 17 cell induction by transforming-growth factorbeta is mediated by suppression of eomesodermin. Immunity 34, 741-754.
25. Kamizono, S., Hanada, T.,Yasukawa, H., Minoguchi, S., Kato, R., Minoguchi, M., Hattori, K., Hatakeyama, S., Yada, M., Morita, S., Kitamura, T., Kato, H., Nakayama, K. I., and Yoshimura,A. (2001). The SOCS box of SOCS-1 accelerates ubiquitindependent proteolysis of TEL-JAK2. J. Biol. Chem. 276, 12530-12538.
26. Kamura, T., Maenaka, K., Kotoshiba, S., Matsumoto, M., Kohda, D., Conaway, R. C., Conaway, J. W., and Nakayama, K. I. (2004). VHLbox and SOCS-box domains determine binding specificity for Cul2Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 18, 3055-3065.
27. Kimura, A., Kinjyo, I., Matsumura, Y., Mori, H., Mashima, R., Harada, M., Chien, K. R., Yasukawa, H., and Yoshimura, A. (2004). SOCS3 is a physiological negative regulator for granulopoiesis and granulocyte colony-stimulating factor receptor signaling. J. Biol. Chem. 279, 6905-6910.
28. Kinjyo, I., Hanada, T., Inagaki-Ohara, K., Mori, H., Aki, D., Ohishi, M., Yoshida, H., Kubo, M., and Yoshimura, A. (2002). SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity 17, 583-591.
29. Kinjyo, I., Inoue, H., Hamano, S., Fukuyama, S., Yoshimura, T., Koga, K., Takaki, H., Himeno, K., Takaesu, G., Kobayashi, T., Yoshimura, A. (2006). Loss of SOCS3 in T helper cells resulted in reduced immune responses and hyperproduction of interleukin 10 and transforming growth factor-beta 1. J. Exp. Med. 203, 1021-1031.
30. Kobayashi, T., Takaesu, G., and Yoshimura, A. (2006). Mal-function of TLRs by SOCS. Nat. Immunol. 7, 123-124.
31. Koga, K., Takaesu, G., Yoshida, R., Nakaya, M., Kobayashi, T., Kinjyo, I., and Yoshimura, A. (2009). Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein. Immunity 30, 372-383.
32. Kubo,M.,Hanada,T.,andYoshimura,A. (2003). Suppressors of cytokine signaling and immunity. Nat. Immunol. 4, 1169-1176.
33. Lehmann, U., Schmitz, J., Weissenbach, M., Sobota, R. M., Hortner, M., Friederichs,K.,Behrmann,I.,Tsiaris, W., Sasaki, A., Schneider-Mergener, J., Yoshimura, A., Neel, B. G., Heinrich, P. C., and Schaper, F. (2003). SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130. J. Biol. Chem. 278, 661-671.
34. Li, Y., Chu, N., Rostami, A., and Zhang, G. X. (2006). Dendritic cells transduced with SOCS-3 exhibit a tolerogenic/DC2 phenotype that directs type 2 Th cell differentiation in vitro and in vivo. J. Immunol. 177, 1679-1688.
35. Liu,Y., Stewart, K. N., Bishop, E., Marek, C. J.,Kluth,D. C.,Rees,A. J.,andWilson, H. M. (2008). Unique expression of suppressor of cytokine signaling 3 is essential for classical macrophage activation in rodents in vitro and in vivo. J. Immunol. 180, 6270-6278.
36. Lu, L. F., Boldin, M. P., Chaudhry, A., Lin, L. L., Taganov, K. D., Hanada, T., Yoshimura, A., Baltimore, D., and Rudensky, A. Y. (2010). Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142, 914-929.
37. Lu, Y., Fukuyama, S., Yoshida, R., Kobayashi, T., Saeki, K., Shiraishi, H., Yoshimura, A., and Takaesu, G. (2006). Loss of SOCS3 gene expression converts STAT3 function from anti-apoptotic to pro-apoptotic. J. Biol. Chem. 281, 36683-36690.
38. Lu, L. F., Thai, T. H., Calado, D. P., Chaudhry, A., Kubo, M., Tanaka, K., Loeb, G. B., Lee, H., Yoshimura, A., Rajewsky, K., and Rudensky, A. Y. (2009). Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30, 80-91.
39. Madonna, S., Scarponi, C., De Pita, O., and Albanesi, C. (2008). Suppressor of cytokine signaling 1 inhibits IFN-gamma inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation. FASEB J. 22, 3287-3297.
40. Marine, J. C., Topham, D. J., McKay, C., Wang, D., Parganas, E., Stravopodis, D., Yoshimura, A., and Ihle, J. N. (1999). SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell 98, 609-616.
41. Masuhara, M., Sakamoto, H., Matsumoto, A., Suzuki, R., Yasukawa, H., Mitsui, K., Wakioka, T., Tanimura, S., Sasaki, A., Misawa, H., Yokouchi, M., Ohtsubo, M., and Yoshimura, A (1997). Cloning and characterization of novel CIS family genes. Biochem. Biophys. Res. Commun. 239, 439-446.
42. Matsumoto, A., Seki, Y., Kubo, M., Ohtsuka, S., Suzuki, A., Hayashi, I., Tsuji, K., Nakahata, T., Okabe, M.,Yamada, S., and Yoshimura, A. (1999). Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice. Mol. Cell. Biol. 19, 6396-6407.
43. Matsumura, Y., Kobayashi, T., Ichiyama, K.,Yoshida, R., Hashimoto, M., Takimoto, T., Tanaka, K., Chinen, T., Shichita, T., Wyss-Coray, T., Sato, K., and Yoshimura, A. (2007). Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J. Immunol. 179, 2170-2179.
44. Mori, H., Hanada, R., Hanada, T., Aki, D.,Mashima,R.,Nishinakamura,H., Torisu, T., Chien, K. R., Yasukawa, H., and Yoshimura, A. (2004). Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nat. Med. 10, 739-743.
45. Mori, T., Miyamoto, T., Yoshida, H., Asakawa, M., Kawasumi, M., Kobayashi, T., Morioka, H., Chiba, K., Toyama, Y., and Yoshimura, A. (2011). IL-1{beta} and TNF{alpha}initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis. Int. Immunol. 23, 701-712.
46. Moriwaki, A., Inoue, H., Nakano, T., Matsunaga, Y., Matsuno, Y., Matsumoto, T., Fukuyama, S., Kan, O. K., Matsumoto, K., TsudaEguchi, M., Nagakubo, D., Yoshie, O., Yoshimura, A., Kubo, M., and Nakanishi, Y. (2011). T cell treatment with small interfering RNA for suppressor of cytokine signaling 3 modulates allergic airway responses in a murine model of asthma. Am. J. Respir. Cell Mol. Biol. 44, 448-455.
47. Mostecki, J., Cassel, S. L., Klimecki, W. T., Stern, D. A., Knisz, J., Iwashita, S., Graves, P., Miller, R. L., van Peer, M., Halonen, M., Martinez, F. D., Vercelli, D., and Rothman, P. B. (2011). A SOCS-1 promoter variant is associated with total serum IgE levels. J. Immunol. 187, 2794-2802.
48. Mottok, A., Renne, C., Seifert, M., Oppermann, E., Bechstein, W., Hansmann, M. L., Kuppers, R., and Brauninger, A. (2009). Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of Bcell lymphoma entities. Blood 114, 4503-4506.
49. Murray, P. J., and Wynn, T. A. (2011). Obstacles and opportunities for understanding macrophage polarization. J. Leukoc. Biol. 89, 557-563.
50. Naka, T., Narazaki, M., Hirata, M., Matsumoto, T., Minamoto, S., Aono, A., Nishimoto, N., Kajita, T., Taga, T., Yoshizaki, K., Akira, S., and Kishimoto, T. (1997). Structure and function of a new STATinduced STAT inhibitor. Nature 387, 924-929.
51. Nakaya, M., Hamano, S., Kawasumi, M., Yoshida, H., Yoshimura, A., and Kobayashi, T. (2011). Aberrant IL-4 production by SOCS3over-expressing T cells during infection with Leishmania major exacerbates disease manifestations. Int. Immunol. 23, 195-202.
52. Nakaya, M., Hashimoto, M., Nakagawa, R., Wakabayashi, Y., Ishizaki, T., Takada, I., Komai, K.,Yoshida, H., and Yoshimura, A. (2009). SOCS3 in T and NKT cells negatively regulates cytokine production and ameliorates ConA-induced hepatitis. J. Immunol. 183, 7047-7053.
53. Ogata, H., Chinen, T., Yoshida, T., Kinjyo, I., Takaesu, G., Shiraishi, H., Iida, M., Kobayashi, T., and Yoshimura, A. (2006a). Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta1 production. Oncogene 25, 2520-2530.
54. Ogata, H., Kobayashi, T., Chinen, T., Takaki, H., Sanada, T., Minoda, Y., Koga, K., Takaesu, G., Maehara, Y., Iida, M., and Yoshimura, A. (2006b). Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology 131, 179-193.
55. Okumura, A., Pitha, P. M., Yoshimura, A., and Harty, R. N. (2010). Interaction between Ebola virus glycoprotein and host toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J. Virol. 84, 27-33.
56. O'Shea, J. J., Gadina, M., and Schreiber, R. D. (2002). Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell 109(Suppl.), S121- S131.
57. Pellegrini, M., Calzascia, T., Toe, J. G., Preston, S. P., Lin, A. E., Elford, A. R., Shahinian, A., Lang, P. A., Lang, K. S., Morre, M., Assouline, B., Lahl, K., Sparwasser, T., Tedder, T. F., Paik, J. H., DePinho, R. A., Basta, S., Ohashi, P. S., and Mak, T. W. (2011). IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell 144, 601-613.
58. Russell,R. C.,Sufan,R. I.,Zhou,B.,Heir, P., Bunda, S., Sybingco, S. S., Greer, S. N., Roche, O., Heathcote, S. A., and Chow, V. W. (2011). Loss of JAK2 regulation via a heterodimeric VHLSOCS1 E3 ubiquitin ligase underlies Chuvash polycythemia. Nat. Med. 17, 845-853.
59. Sachithanandan, N., Graham, K. L., Galic, S., Honeyman, J. E., Fynch, S. L., Hewitt, K. A., Steinberg, G. R., and Kay, T. W. (2011). Macrophage deletion of SOCS1 increases sensitivity to LPS and palmitic acid and results in systemic inflammation and hepatic insulin resistance. Diabetes 60, 2023-2031.
60. Sasaki, A., Yasukawa, H., Shouda, T., Kitamura, T., Dikic, I., and Yoshimura, A. (2000). CIS3/SOCS3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J. Biol. Chem. 275, 29338-29347.
61. Sasaki, A., Yasukawa, H., Suzuki, A., Kamizono, S., Syoda, T., Kinjyo, I., Sasaki, M., Johnston, J. A., and Yoshimura, A. (1999). Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain. Genes Cells 4, 339-351.
62. Sawa, S., Kamimura, D., Jin, G. H., Morikawa, H., Kamon, H., Nishihara,M.,Ishihara,K.,Murakami,M., and Hirano, T. (2006) Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells. J. Exp. Med. 203, 1459-1470.
63. Schmitz, J., Weissenbach, M., Haan, S., Heinrich, P. C., and Schaper, F. (2000). SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130. J. Biol. Chem. 275, 12848-12856.
64. Seki, Y., Inoue, H., Nagata, N., Hayashi, K., Fukuyama, S., Matsumoto, K., Komine, O., Hamano, S., Himeno, K., Inagaki-Ohara, K., Cacalano, N., O'Garra, A., Oshida, T., Saito, H., Johnston, J. A., Yoshimura, A., and Kubo, M. (2003). SOCS-3 regulates onset and maintenance of T(H)2mediated allergic responses. Nat. Med. 9, 1047-1054.
65. Shouda, T., Yoshida, T., Hanada, T., Wakioka, T., Oishi, M., Miyoshi, K., Komiya, S., Kosai, K., Hanakawa, Y., Hashimoto, K., Nagata, K., and Yoshimura, A. (2001). Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J. Clin. Invest. 108, 1781-1788.
66. Starr, R., Willson, T. A., Viney, E. M., Murray, L. J., Rayner, J. R., Jenkins, B. J., Gonda, T. J., Alexander, W. S., Metcalf, D., Nicola, N. A., and Hilton, D. J. (1997). A family of cytokine-inducible inhibitors of signalling. Nature 387, 917-921.
67. Stutz, A., Kessler, H., Kaschel, M. E., Meissner, M., and Dalpke, A. H. (2012). Cell invasion and strain dependent induction of suppressor of cytokine signaling-1 by Toxoplasma gondii. Immunobiology 217, 28-36.
68. Suzuki, A., Hanada, T., Mitsuyama, K., Yoshida, T., Kamizono, S., Hoshino, T., Kubo, M., Yamashita, A., Okabe, M., Takeda, K., Akira, S., Matsumoto, S., Toyonaga, A., Sata, M., and Yoshimura, A (2001). CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. J. Exp. Med. 193, 471-481.
69. Takahashi, R., Nishimoto, S., Muto, G., Sekiya, T., Tamiya, T., Kimura, A., Morita, R., Asakawa, M., Chinen, T., and Yoshimura, A. (2011). SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3 expression as well as IFN-{gamma} and IL-17A production. J. Exp. Med. 208, 2055-2067.
70. Taleb, S., Romain, M., Ramkhelawon, B., Uyttenhove, C., Pasterkamp, G., Herbin, O., Esposito, B., Perez, N., Yasukawa, H., Van, Snick, J., Yoshimura, A., Tedgui, A., and Mallat, Z. (2009). Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J. Exp. Med. 206, 2067-2077.
71. Tamiya, T., Kashiwagi, I., Takahashi, R., Yasukawa, H., and Yoshimura, A. (2011). Suppressors of cytokine signaling (SOCS) proteins and JAK/STAT pathways: regulation of T-cell inflammation by SOCS1 and SOCS3. Arterioscler. Thromb. Vasc. Biol. 31, 980-985.
72. Tanaka, K., Ichiyama, K., Hashimoto, M., Yoshida, H., Takimoto, T., Takaesu, G., Torisu, T., Hanada, T., Yasukawa, H., Fukuyama, S., Inoue, H., Nakanishi, Y., Kobayashi, T., and Yoshimura, A. (2008). Loss of suppressor of cytokine signaling 1 in helper T cells leads to defective Th17 differentiation by enhancing antagonistic effects of IFN-gamma on STAT3 and Smads. J. Immunol. 180, 3746-3756.
73. Torisu, T., Nakaya, M., Watanabe, S., Hashimoto, M.,Yoshida, H., Chinen, T.,Yoshida, R., Okamoto, F., Hanada, T.,Torisu,K.,Takaesu,G.,Kobayashi, T., Yasukawa, H., and Yoshimura, A. (2008). Suppressor of cytokine signaling 1 protects mice against concanavalin A-induced hepatitis by inhibiting apoptosis. Hepatology 47, 1644-1654.
74. Torisu, T., Sato, N., Yoshiga, D., Kobayashi, T.,Yoshioka, T., Mori, H., Iida, M., and Yoshimura, A. (2007). The dual function of hepatic SOCS3 in insulin resistance in vivo. Genes Cells 12, 143-154.
75. Wang, Y. C., He, F., Feng, F., Liu, X. W., Dong, G. Y., Qin, H. Y., Hu, X. B., Zheng, M. H., Liang, L., Feng, L., Liang, Y. M., and Han, H. (2010). Notch signaling determines the M1 versus M2 polarization of macrophages in antitumor immune responses. Cancer Res. 70, 4840-4849.
76. Whitmarsh, R. J., Gray, C. M., Gregg, B., Christian, D. A., May, M. J., Murray, P. J., and Hunter, C. A. (2011). A Critical Role for SOCS3 in Innate Resistance to Toxoplasma gondii. Cell Host Microbe 10, 224-236.
77. Wong, P. K., Egan, P. J., Croker, B. A., O'Donnell, K., Sims, N. A., Drake, S., Kiu, H., McManus, E. J., Alexander, W. S., Roberts, A. W., and Wicks, I. P. (2006). SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J. Clin. Invest. 116, 1571-1581.
78. Yamamoto, K., Yamaguchi, M., Miyasaka, N., and Miura, O. (2003). SOCS-3 inhibits IL-12induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit. Biochem. Biophys. Res. Commun. 310, 1188-1193.
79. Yasukawa, H., Misawa, H., Sakamoto, H., Masuhara, M., Sasaki, A., Wakioka, T., Ohtsuka, S., Imaizumi, T., Matsuda, T., Ihle, J. N., and Yoshimura, A. (1999). The JAKbinding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop. EMBO J. 18, 1309-1320.
80. Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., Hirano, T., Chien, K. R., and Yoshimura, A. (2003). IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat. Immunol. 4, 551-556.
81. Yoshida, T., Ogata, H., Kamio, M., Joo, A., Shiraishi, H., Tokunaga, Y., Sata, M., Nagai, H., and Yoshimura, A. (2004). SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis. J. Exp. Med. 199, 1701-1707.
82. Yoshimura, A. (2006). Signal transduction of inflammatory cytokines and tumor development. Cancer Sci. 97, 439-447.
83. Yoshimura, A., Naka, T., and Kubo, M. (2007). SOCS proteins, cytokine signalling and immune regulation. Nat. Rev. Immunol. 7, 454-465.
84. Yoshimura, A., Ohkubo, T., Kiguchi, T., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Hara, T., and Miyajima, A. (1995). A novel cytokineinducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. EMBO J. 14, 2816-2826.
85. Zhang, R., Dhillon, H., Yin, H., Yoshimura, A., Lowell, B. B., Maratos-Flier, E., and Flier, J. S. (2008). Selective inactivation of Socs3 in SF1 neurons improves glucose homeostasis without affecting body weight. Endocrinology 149, 5654-5661.
86. Zhang, Y., Ma, C. J., Ni, L., Zhang, C. L., Wu, X. Y., Kumaraguru, U., Li, C. F., Moorman, J. P., and Yao, Z. Q. (2011). Cross-talk between programmed death-1 and suppressor of cytokine signaling-1 in inhibition of IL-12 production by monocytes/macrophages in hepatitis C virus infection. J. Immunol. 186, 3093-3103.