Abstract
Several family members of Krüppel-like factors (KLFs) are found in lymphocytes, and their expression is tightly regulated during development and differentiation. The related factors KLF2 and KLF4 have been suggested to promote lymphocyte “quiescence” by inducing withdrawal of cells from the cell cycle. Although the physiological role of KLF2 in cell cycle control in lymphocytes is currently unclear, it is potentially due to redundancy between related KLFs. On the other hand, there is growing evidence that individual KLFs regulate migration of lymphocytes (and other cells) during normal homeostasis of the immune system and in inflammatory situations. In addition to KLF2 and KLF4, the roles of KLF10 and KL13 in lymphocytes are briefly discussed.
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References
Ahn, Y.T., Huang, B., McPherson, L., Clayberger, C., and Krensky, A.M. (2007). Dynamic interplay of transcriptional machinery and chromatin regulates “late” expression of the chemokine RANTES in T lymphocytes. Molecular and Cellular Biology 27, 253–266.
Bai, A., Hu, H., Yeung, M., and Chen, J. (2007). Kruppel-like factor 2 controls T cell trafficking by activating L-selectin (CD62L) and sphingosine-1-phosphate receptor 1 transcription. J Immunol 178, 7632–7639.
Bettelli, E., Korn, T., and Kuchroo, V.K. (2007). Th17: the third member of the effector T cell trilogy. Current Opinion in Immunology 19, 652–657.
Buckley, A.F., Kuo, C.T., and Leiden, J.M. (2001). Transcription factor LKLF is sufficient to program T cell quiescence via a c-Myc—dependent pathway. Nature Immunology 2, 698–704.
Carlson, C.M., Endrizzi, B.T., Wu, J., Ding, X., Weinreich, M.A., Walsh, E.R., Wani, M.A., Lingrel, J.B., Hogquist, K.A., and Jameson, S.C. (2006). Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 442, 299–302.
Conkright, M.D., Wani, M.A., and Lingrel, J.B. (2001). Lung Kruppel-like factor contains an autoinhibitory domain that regulates its transcriptional activation by binding WWP1, an E3 ubiquitin ligase. J Biol Chem 276, 29299–29306.
Cornish, G.H., Sinclair, L.V., and Cantrell, D.A. (2006). Differential regulation of T-cell growth by IL-2 and IL-15. Blood 108, 600–608.
Cyster, J.G. (2005). Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs. Annu Rev Immunol 23, 127–159.
Dong, C. (2008). TH17 cells in development: an updated view of their molecular identity and genetic programming. Nature reviews 8, 337–348.
Endrizzi, B.T., and Jameson, S.C. (2003). Differential role for IL-7 in inducing lung Kruppel-like factor (Kruppel-like factor 2) expression by naive versus activated T cells. Int Immunol 15, 1341–1348.
Fabre, S., Carrette, F., Chen, J., Lang, V., Semichon, M., Denoyelle, C., Lazar, V., Cagnard, N., Dubart-Kupperschmitt, A., Mangeney, M., et al. (2008). Forkhead Box O1 Regulates L-Selectin and a Network of Human T-Cell Homing Molecules Downstream of Phosphatidylinositol 3-Kinase. J Immunol IN PRESS.
Fruman, D.A. (2004). Phosphoinositide 3-kinase and its targets in B-cell and T-cell signaling. Current opinion in immunology 16, 314–320.
Glynne, R., Ghandour, G., Rayner, J., Mack, D.H., and Goodnow, C.C. (2000). B-lymphocyte quiescence, tolerance and activation as viewed by global gene expression profiling on microarrays. Immunol Rev 176, 216–246.
Good, K.L., and Tangye, S.G. (2007). Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses. Proc Natl Acad Sci U S A 104, 13420–13425.
Grayson, J.M., Murali-Krishna, K., Altman, J.D., and Ahmed, R. (2001). Gene expression in antigen-specific CD8+ T cells during viral infection. J Immunol 166, 795–799.
Haaland, R.E., Yu, W., and Rice, A.P. (2005). Identification of LKLF-regulated genes in quiescent CD4+ T lymphocytes. Mol Immunol 42, 627–641.
Haldar, S.M., Ibrahim, O.A., and Jain, M.K. (2007). Kruppel-like Factors (KLFs) in muscle biology. J Mol Cell Cardiol 43, 1–10.
Huang, B., Ahn, Y.T., McPherson, L., Clayberger, C., and Krensky, A.M. (2007). Interaction of PRP4 with Kruppel-like factor 13 regulates CCL5 transcription. J Immunol 178, 7081–7087.
Kabashima, K., Haynes, N.M., Xu, Y., Nutt, S.L., Allende, M.L., Proia, R.L., and Cyster, J.G. (2006). Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism. The Journal of Experimental Medicine 203, 2683–2690.
Kaczynski, J., Cook, T., and Urrutia, R. (2003). Sp1− and Kruppel-like transcription factors. Genome Biol 4, 206.
Kharas, M.G., Yusuf, I., Scarfone, V.M., Yang, V.W., Segre, J.A., Huettner, C.S., and Fruman, D.A. (2007). KLF4 suppresses transformation of pre-B cells by ABL oncogenes. Blood 109, 747–755.
Klaewsongkram, J., Yang, Y., Golech, S., Katz, J., Kaestner, K.H., and Weng, N.P. (2007). Kruppel-like factor 4 regulates B cell number and activation-induced B cell proliferation. J Immunol 179, 4679–4684.
Kuo, C.T., and Leiden, J.M. (1999). Transcriptional regulation of T lymphocyte development and function. Annu Rev Immunol 17, 149–187.
Kuo, C.T., Veselits, M.L., Barton, K.P., Lu, M.M., Clendenin, C., and Leiden, J.M. (1997a). The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev 11, 2996–3006.
Kuo, C.T., Veselits, M.L., and Leiden, J.M. (1997b). LKLF: A transcriptional regulator of singlepositive T cell quiescence and survival. Science 277, 1986–1990.
Matloubian, M., Lo, C.G., Cinamon, G., Lesneski, M.J., Xu, Y., Brinkmann, V., Allende, M.L., Proia, R.L., and Cyster, J.G. (2004). Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360.
McCaughtry, T.M., Wilken, M.S., and Hogquist, K.A. (2007). Thymic emigration revisited. The Journal of Experimental Medicine 204, 2513–2520.
Mick, V.E., Starr, T.K., McCaughtry, T.M., McNeil, L.K., and Hogquist, K.A. (2004). The regulated expression of a diverse set of genes during thymocyte positive selection in vivo. J Immunol 173, 5434–5444.
Narla, G., Heath, K.E., Reeves, H.L., Li, D., Giono, L.E., Kimmelman, A.C., Glucksman, M.J., Narla, J., Eng, F.J., Chan, A.M., et al. (2001). KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science 294, 2563–2566.
Nikolcheva, T., Pyronnet, S., Chou, S.Y., Sonenberg, N., Song, A., Clayberger, C., and Krensky, A.M. (2002). A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes. The Journal of Clinical Investigation 110, 119–126.
Outram, S.V., Gordon, A.R., Hager-Theodorides, A.L., Metcalfe, J., Crompton, T., and Kemp, P. (2008). KLF13 influences multiple stages of both B and T cell development. Cell Cycle 7, 2047–2055.
Parmar, K.M., Larman, H.B., Dai, G., Zhang, Y., Wang, E.T., Moorthy, S.N., Kratz, J.R., Lin, Z., Jain, M.K., Gimbrone, M.A., Jr., and Garcia-Cardena, G. (2006). Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. The Journal of Clinical Investigation 116, 49–58.
Riou, C., Yassine-Diab, B., Van grevenynghe, J., Somogyi, R., Greller, L.D., Gagnon, D., Gimmig, S., Wilkinson, P., Shi, Y., Cameron, M.J., et al. (2007). Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells. The Journal of Experimental Medicine 204, 79–91.
Rowland, B.D., Bernards, R., and Peeper, D.S. (2005). The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol 7, 1074–1082.
Rowland, B.D., and Peeper, D.S. (2006). KLF4, p21 and context-dependent opposing forces in cancer. Nat Rev Cancer 6, 11–23.
Sallusto, F., Geginat, J., and Lanzavecchia, A. (2004). Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22, 745–763.
Schober, S.L., Kuo, C.T., Schluns, K.S., Lefrancois, L., Leiden, J.M., and Jameson, S.C. (1999). Expression of the transcription factor lung Kruppel-like factor is regulated by cytokines and correlates with survival of memory T cells in vitro and in vivo. J Immunol 163, 3662–3667.
Schuh, W., Meister, S., Herrmann, K., Bradl, H., and Jack, H.M. (2008). Transcriptome analysis in primary B lymphoid precursors following induction of the pre-B cell receptor. Mol Immunol 45, 362–375.
Sebzda, E., Zou, Z., Lee, J.S., Wang, T., and Kahn, M.L. (2008). Transcription factor KLF2 regulates the migration of naive T cells by restricting chemokine receptor expression patterns. Nature Immunology 9, 292–300.
Shie, J.L., Chen, Z.Y., Fu, M., Pestell, R.G., and Tseng, C.C. (2000). Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif. Nucleic Acids Res 28, 2969–2976.
Sinclair, L.V., Finlay, D., Feijoo, C., Cornish, G.H., Gray, A., Ager, A., Okkenhaug, K., Hagenbeek, T.J., Spits, H., and Cantrell, D.A. (2008). Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nature Immunology 9, 513–521.
Sohn, S.J., Li, D., Lee, L.K., and Winoto, A. (2005). Transcriptional regulation of tissue-specific genes by the ERK5 mitogen-activated protein kinase. Molecular and Cellular Biology 25, 8553–8566.
Song, A., Chen, Y.F., Thamatrakoln, K., Storm, T.A., and Krensky, A.M. (1999). RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. Immunity 10, 93–103.
Song, A., Patel, A., Thamatrakoln, K., Liu, C., Feng, D., Clayberger, C., and Krensky, A.M. (2002). Functional domains and DNA-binding sequences of RFLAT-1/KLF13, a Kruppel-like transcription factor of activated T lymphocytes. J Biol Chem 277, 30055–30065.
Suzuki, T., Aizawa, K., Matsumura, T., and Nagai, R. (2005). Vascular implications of the Kruppel-like family of transcription factors. Arterioscler Thromb Vasc Biol 25, 1135–1141.
Turner, J., and Crossley, M. (1999). Mammalian Kruppel-like transcription factors: more than just a pretty finger. Trends Biochem Sci 24, 236–240.
van Zelm, M.C., van der Burg, M., de Ridder, D., Barendregt, B.H., de Haas, E.F., Reinders, M.J., Lankester, A.C., Revesz, T., Staal, F.J., and van Dongen, J.J. (2005). Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression. J Immunol 175, 5912–5922.
Venuprasad, K., Huang, H., Harada, Y., Elly, C., Subramaniam, M., Spelsberg, T., Su, J., and Liu, Y.C. (2008). The E3 ubiquitin ligase Itch regulates expression of transcription factor Foxp3 and airway inflammation by enhancing the function of transcription factor TIEG1. Nature Immunology 9, 245–253.
von Andrian, U.H., and Mempel, T.R. (2003). Homing and cellular traffic in lymph nodes. Nature Reviews 3, 867–878.
Wu, J., and Lingrel, J.B. (2004). KLF2 inhibits Jurkat T leukemia cell growth via upregulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1. Oncogene 23, 8088–8096.
Yasunaga, J., Taniguchi, Y., Nosaka, K., Yoshida, M., Satou, Y., Sakai, T., Mitsuya, H., and Matsuoka, M. (2004). Identification of aberrantly methylated genes in association with adult T-cell leukemia. Cancer Res 64, 6002–6009.
Yusuf, I., and Fruman, D.A. (2003). Regulation of quiescence in lymphocytes. Trends Immunol 24, 380–386.
Yusuf, I., Kharas, M.G., Chen, J., Peralta, R.Q., Maruniak, A., Sareen, P., Yang, V.W., Kaestner, K.H., and Fruman, D.A. (2008). KLF4 is a FOXO target gene that suppresses B cell proliferation. Int Immunol 20, 671–681.
Zhang, W., Geiman, D.E., Shields, J.M., Dang, D.T., Mahatan, C.S., Kaestner, K.H., Biggs, J.R., Kraft, A.S., and Yang, V.W. (2000). The gut-enriched Kruppel-like factor (Kruppel-like factor 4) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter. J Biol Chem 275, 18391–18398.
Zhang, X., Srinivasan, S.V., and Lingrel, J.B. (2004). WWP1-dependent ubiquitination and degradation of the lung Kruppel-like factor, KLF2. Biochem Biophys Res Commun 316, 139–148.
Zhou, M., McPherson, L., Feng, D., Song, A., Dong, C., Lyu, S.C., Zhou, L., Shi, X., Ahn, Y.T., Wang, D., et al. (2007). Kruppel-like transcription factor 13 regulates T lymphocyte survival in vivo. J Immunol 178, 5496–5504.
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Takada, K., Hogquist, K.A., Jameson, S.C. (2009). Roles of Krüppel-like Factors in Lymphocytes. In: Nagai, R., Friedman, S.L., Kasuga, M. (eds) The Biology of Krüppel-like Factors. Springer, Tokyo. https://doi.org/10.1007/978-4-431-87775-2_7
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DOI: https://doi.org/10.1007/978-4-431-87775-2_7
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