IKKα is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells

FASEB Journal

Volumn 29, Issue 2, 2015, Pages 443-454

  Chen, Xin ^a,b,c   Willette Brown, Jami ^b   Wu, Xueqiang ^b   Hu, Ya ^b   Howard, O M Zack ^b   Hu, Yinling ^b   Oppenheim, Joost J ^b  

^a FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^b NATIONAL CANCER INSTITUTE   (United States)

^c University of Macau   (Macao)

Author keywords

Colitis; Foxp3; Lymphopenic mouse; Proliferation

Indexed keywords

I KAPPA B KINASE ALPHA; RAG1 PROTEIN; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; HOMEODOMAIN PROTEIN; I KAPPA B KINASE; LYMPHOCYTE ANTIGEN RECEPTOR; RAG-1 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CD4+ T LYMPHOCYTE; CELL EXPANSION; CELL FUNCTION; CELL ISOLATION; CELL POPULATION; CELL PROLIFERATION; CELL STIMULATION; COLITIS; CONTROLLED STUDY; EFFECTOR CELL; HOMEOSTASIS; IN VITRO STUDY; IN VIVO STUDY; LYMPHOID TISSUE; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; STIMULATION; THYMUS; ANIMAL; C57BL MOUSE; CYTOLOGY; FLOW CYTOMETRY; GENETICS; IMMUNOSUPPRESSIVE TREATMENT; KNOCKOUT MOUSE; METABOLISM; MUTATION; PHYSIOLOGY; SIGNAL TRANSDUCTION;

MUS;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELL PROLIFERATION; COLITIS; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; HOMEODOMAIN PROTEINS; HOMEOSTASIS; I-KAPPA B KINASE; IMMUNOSUPPRESSION; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MUTATION; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY; THYMUS GLAND;

EID: 84928344042     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.14-259564     Document Type: Article

References (46)

1. Zhu, J., Yamane, H., and Paul, W. E. (2010) Differentiation of effector CD4 T cell populations (∗). Annu. Rev. Immunol. 28, 445-489
2. Kaech, S. M., Wherry, E. J., and Ahmed, R. (2002) Effector and memory T-cell differentiation: implications for vaccine development. Nat. Rev. Immunol. 2, 251-262
3. Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. (2008) Regulatory T cells and immune tolerance. Cell 133, 775-787
4. Zou, W. (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol. 6, 295-307
5. Dev, A., Iyer, S., Razani, B., and Cheng, G. (2011) NF-κB and innate immunity. Curr. Top. Microbiol. Immunol. 349, 115-143
6. Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M., and Karin, M. (1997) The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 91, 243-252
7. Häcker, H., and Karin, M. (2006) Regulation and function of IKK and IKK-related kinases. Sci. STKE 2006, re13
8. Senftleben, U., Cao, Y., Xiao, G., Greten, F. R., Krähn, G., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S. C., and Karin, M. (2001) Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 293, 1495-1499
9. Yamamoto, Y., Verma, U. N., Prajapati, S., Kwak, Y. T., and Gaynor, R. B. (2003) Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature 423, 655-659
10. Chen, X., Bäumel, M., Männel, D. N., Howard, O. M., and Oppenheim, J. J. (2007) Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells. J. Immunol. 179, 154-161
11. Chen, X., Subleski, J. J., Hamano, R., Howard, O. M., Wiltrout, R. H., and Oppenheim, J. J. (2010) Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood. Eur. J. Immunol. 40, 1099-1106
12. Chen, X., Subleski, J. J., Kopf, H., Howard, O. M., Männel, D. N., and Oppenheim, J. J. (2008) Cutting edge: expression of TNFR2 defines a maximally suppressive subset of mouse CD4+CD25+ FoxP3+ T regulatory cells: applicability to tumor-infiltrating T regulatory cells. J. Immunol. 180, 6467-6471
13. Chen, X., Wu, X., Zhou, Q., Howard, O. M., Netea, M. G., and Oppenheim, J. J. (2013) TNFR2 is critical for the stabilization of the CD4+Foxp3+ regulatory T. cell phenotype in the inflammatory environment. J. Immunol. 190, 1076-1084
14. Rauert, H., Wicovsky, A., Müller, N., Siegmund, D., Spindler, V., Waschke, J., Kneitz, C., and Wajant, H. (2010) Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2). J. Biol. Chem. 285, 7394-7404
15. Li, L., Ruan, Q., Hilliard, B., Devirgiliis, J., Karin, M., and Chen, Y. H. (2011) Transcriptional regulation of the Th17 immune response by IKK(alpha). J. Exp. Med. 208, 787-796
16. Chen, X., Hamano, R., Subleski, J. J., Hurwitz, A. A., Howard, O. M., and Oppenheim, J. J. (2010) Expression of costimulatory TNFR2 induces resistance of CD4+FoxP3- conventional T cells to suppression by CD4+FoxP3+ regulatory T cells. J. Immunol. 185, 174-182
17. Mahmud, S. A., Manlove, L. S., Schmitz, H. M., Xing, Y., Wang, Y., Owen, D. L., Schenkel, J. M., Boomer, J. S., Green, J. M., Yagita, H., Chi, H., Hogquist, K. A., and Farrar, M. A. (2014) Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat. Immunol. 15, 473-481
18. Sun, S. C. (2011) Non-canonical NF-κB signaling pathway. Cell Res. 21, 71-85
19. Kaisho, T., Takeda, K., Tsujimura, T., Kawai, T., Nomura, F., Terada, N., and Akira, S. (2001) IkappaB kinase alpha is essential for mature B cell development and function. J. Exp. Med. 193, 417-426
20. Ren, H., Schmalstieg, A., van Oers, N. S., and Gaynor, R. B. (2002) I-kappa B kinases alpha and beta have distinct roles in regulating murine T cell function. J. Immunol. 168, 3721-3731
21. Liu, B., Xia, X., Zhu, F., Park, E., Carbajal, S., Kiguchi, K., DiGiovanni, J., Fischer, S. M., and Hu, Y. (2008) IKKalpha is required to maintain skin homeostasis and prevent skin cancer. Cancer Cell 14, 212-225
22. Institute of Laboratory Animal Research, Commission on Life Sciences, National Research Council. (1996) Guide for Care and Use of Laboratory Animals, National Academy Press, Washington, D.C.
23. Griseri, T., Asquith, M., Thompson, C., and Powrie, F. (2010) OX40 is required for regulatory T cell-mediated control of colitis. J. Exp. Med. 207, 699-709
24. Housley, W. J., Adams, C. O., Nichols, F. C., Puddington, L., Lingenheld, E. G., Zhu, L., Rajan, T. V., and Clark, R. B. (2011) Natural but not inducible regulatory T cells require TNF-alpha signaling for in vivo function. J. Immunol. 186, 6779-6787
25. Yurchenko, E., Shio, M. T., Huang, T. C., Da Silva Martins, M., Szyf, M., Levings, M. K., Olivier, M., and Piccirillo, C. A. (2012) Inflammation-driven reprogramming of CD4+ Foxp3+ regulatory T cells into pathogenic Th1/Th17 T effectors is abrogated by mTOR inhibition in vivo. PLoS One 7, e35572
26. Duarte, J. H., Zelenay, S., Bergman, M. L., Martins, A. C., and Demengeot, J. (2009) Natural Treg cells spontaneously differentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 39, 948-955
27. Min, B., Yamane, H., Hu-Li, J., and Paul, W. E. (2005) Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms. J. Immunol. 174, 6039-6044
28. Isomura, I., Palmer, S., Grumont, R. J., Bunting, K., Hoyne, G., Wilkinson, N., Banerjee, A., Proietto, A., Gugasyan, R., Wu, L., McNally, A., Steptoe, R. J., Thomas, R., Shannon, M. F., and Gerondakis, S. (2009) c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells. J. Exp. Med. 206, 3001-3014
29. Long, M., Park, S. G., Strickland, I., Hayden, M. S., and Ghosh, S. (2009) Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 31, 921-931
30. Ruan, Q., Kameswaran, V., Tone, Y., Li, L., Liou, H. C., Greene, M. I., Tone, M., and Chen, Y. H. (2009) Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome. Immunity 31, 932-940
31. Zheng, Y., Josefowicz, S., Chaudhry, A., Peng, X. P., Forbush, K., and Rudensky, A. Y. (2010) Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808-812
32. Chang, J. H., Xiao, Y., Hu, H., Jin, J., Yu, J., Zhou, X., Wu, X., Johnson, H. M., Akira, S., Pasparakis, M., Cheng, X., and Sun, S. C. (2012) Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells. Nat. Immunol. 13, 481-490
33. Gückel, E., Frey, S., Zaiss, M. M., Schett, G., Ghosh, S., and Voll, R. E. (2011) Cell-intrinsic NF-κB activation is critical for the development of natural regulatory T cells in mice. PLoS One 6, e20003
34. Zhang, R., Huynh, A., Whitcher, G., Chang, J., Maltzman, J. S., and Turka, L. A. (2013) An obligate cell-intrinsic function for CD28 in Tregs. J. Clin. Invest. 123, 580-593
35. Tai, X., Cowan, M., Feigenbaum, L., and Singer, A. (2005) CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat. Immunol. 6, 152-162
36. Hamano, R., Huang, J., Yoshimura, T., Oppenheim, J. J., and Chen, X. (2011) TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40. Eur. J. Immunol. 41, 2010-2020
37. Sanchez-Valdepenas, C., Martin, A. G., Ramakrishnan, P., Wallach, D., and Fresno, M. (2006) NF-kappaB-inducing kinase is involved in the activation of the CD28 responsive element through phosphorylation of c-Rel and regulation of its transactivating activity. J. Immunol. 176, 4666-4674
38. Corn, R. A., Hunter, C., Liou, H. C., Siebenlist, U., and Boothby, M. R. (2005) Opposing roles for RelB and Bcl-3 in regulation of T-box expressed in T cells, GATA-3, and Th effector differentiation. J. Immunol. 175, 2102-2110
39. Basak, S., Kim, H., Kearns, J. D., Tergaonkar, V., O'Dea, E., Werner, S. L., Benedict, C. A., Ware, C. F., Ghosh, G., Verma, I. M., and Hoffmann, A. (2007) A fourth IkappaB protein within the NF-kappaB signaling module. Cell 128, 369-381
40. Oh, H., and Ghosh, S. (2013) NF-kB: roles and regulation in different CD4(+) T-cell subsets. Immunol. Rev. 252, 41-51
41. Legarda-Addison, D., and Ting, A. T. (2007) Negative regulation of TCR signaling by NF-kappaB2/p100. J. Immunol. 178, 7767-7778
42. Giardino Torchia, M. L., Conze, D. B., Jankovic, D., and Ashwell, J. D. (2013) Balance between NF-kappaB p100 and p52 regulates T cell costimulation dependence. J. Immunol. 190, 549-555
43. Lawrence, T., Bebien, M., Liu, G. Y., Nizet, V., and Karin, M. (2005) IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation. Nature 434, 1138-1143
44. Li, Q., Lu, Q., Bottero, V., Estepa, G., Morrison, L., Mercurio, F., and Verma, I. M. (2005) Enhanced NF-kappaB activation and cellular function in macrophages lacking IkappaB kinase 1 (IKK1). Proc. Natl. Acad. Sci. USA 102, 12425-12430
45. Liu, B., Yang, Y., Chernishof, V., Loo, R. R., Jang, H., Tahk, S., Yang, R., Mink, S., Shultz, D., Bellone, C. J., Loo, J. A., and Shuai, K. (2007) Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity. Cell 129, 903-914
46. Tiemessen, M. M., Jagger, A. L., Evans, H. G., van Herwijnen, M. J., John, S., and Taams, L. S. (2007) CD4+ CD25+ Foxp3+ regulatory T cells induce alternative activation of human monocytes/ macrophages. Proc. Natl. Acad. Sci. USA 104, 19446-19451