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Chemical Compound Review

IL-7     3-(3-bromophenyl)-1- (morpholin-4...

Synonyms: AC1MIDMN, AG-G-14619, CTK5B0908, LS-147546, BRN 0928013, ...
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Disease relevance of IL-7

  • IL-2R gamma is a common gamma chain, gamma c, also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency [1].
  • IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART [2].
  • The antifibrotic activities of IL-7 merit further basic and clinical investigation for the treatment of pulmonary fibrosis [3].
  • Surprisingly, serum osteocalcin levels, a biochemical marker of bone formation, suggested that the bone-sparing effects of IL-7 neutralization were due not only to inhibition of bone resorption, but also to stimulation of bone formation [4].
  • Taken together, these data offer insight into human B cell development as well as B cell dysfunction in advanced HIV disease that may be linked to IL-7-dependent homeostatic events [5].

Psychiatry related information on IL-7


High impact information on IL-7

  • Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis [7].
  • IL-2, IL-15, and IL-7 are cytokines that are critical for regulating lymphoid homeostasis [7].
  • The control of CD4+ memory T cells is more mysterious, with roles reported for IL-7 and/or contact via the TCR [8].
  • Their deaths are prevented in animals by IL-7 and contact with MHC [8].
  • Some factors that control early lymphoid development are discussed, including IL-7 and the Ikaros transcription factors [9].

Chemical compound and disease context of IL-7

  • Remarkably, the IL-12-conditioned CD8 T cells demonstrate increased sensitivity to IL-7 and IL-15, whereby they are rendered "fit" for homeostatic self-renewal as well as augmented CD4-dependent recall responses that are effective at controlling Salmonella infection in vivo [10].
  • While Jak3 SCID patients possess mature peripheral B cells, we demonstrate that the Jak3 tyrosine kinase is also expressed in human pre-B cells and can be activated by the pre-B cell growth factor IL-7 [11].

Biological context of IL-7

  • In agreement with representing a lymphoid primed progenitor, Lin-Sca-1+c-kit+CD34+Flt3+ cells display upregulated IL-7 receptor gene expression [12].
  • IL-7 and IL-7 receptor functions are believed to result in lymphoid cell proliferation and cell maturation, implying signal transduction pathways directly involved in mitogenesis and elaboration of developmentally specific new gene programs [13].
  • By contrast, for expression of more mature action potentials (tetrodotoxin-sensitive) one of the interleukins IL-5, IL-7 or IL-9 must be applied in association with transforming growth factor-alpha after pretreatment with basic fibroblast growth factor [14].
  • The combination of IL-7 and interferons alpha/beta induces bcl-2 down-regulation and cell death by apoptosis [15].
  • Treatment with the immunotoxin in conjunction with agents that activate virus expression without inducing cell division (IL-7 or the non-tumor-promoting phorbol ester prostratin) depleted the bulk of the latent reservoir and left uninfected cells able to respond to subsequent costimulation [16].

Anatomical context of IL-7


Associations of IL-7 with other chemical compounds

  • We conclude that IL-7 is a pivotal upstream target through which estrogen regulates hematopoietic and immune functions that are critical for bone homeostasis [22].
  • Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL-7, they remain responsive to this cytokine, which can reduce their sensitivity to imatinib [23].
  • Tyrosine phosphorylation of several proteins (55 kd, 30 kd, and 24 kd) in HS-27a cells was rapidly increased after incubation with recombinant IL-7 [24].
  • Furthermore, the extent of apoptosis inhibition by IL-7 in vitro quantitatively correlated with early cytoreduction as determined by the prednisone peripheral blood response on day 8 and cytoreduction in the marrow on day 15 (n = 87; P <.05) [25].
  • In comparison to the control cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity [26].

Gene context of IL-7

  • The interleukin-2 receptor (IL-2R) consists of three subunits: the IL-2R alpha, IL-2R beta, and IL-2R gamma chains, the last of which is also used in the receptors for IL-4, IL-7, and IL-9 [27].
  • Thus, in young mice, Bax emerges as an essential protein in the death pathway induced by IL-7 deficiency [28].
  • In this paper, we show that the survival of resting T cells in vitro is promoted by two cytokines, interleukins 4 and 7 (IL-4, IL-7) [29].
  • Finally, these studies are consistent with the hypothesis that the molecular pathogenesis of X-SCID is due primarily to gamma(c)-mediated defects in the IL-7/IL-7R system [30].
  • IL-7-mediated inhibition of TGF-beta signaling was found to be associated with an increase in Smad7, a major inhibitory regulator in the SMAD family [3].

Analytical, diagnostic and therapeutic context of IL-7


  1. Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling. Nakamura, Y., Russell, S.M., Mess, S.A., Friedmann, M., Erdos, M., Francois, C., Jacques, Y., Adelstein, S., Leonard, W.J. Nature (1994) [Pubmed]
  2. IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART. Wang, F.X., Xu, Y., Sullivan, J., Souder, E., Argyris, E.G., Acheampong, E.A., Fisher, J., Sierra, M., Thomson, M.M., Najera, R., Frank, I., Kulkosky, J., Pomerantz, R.J., Nunnari, G. J. Clin. Invest. (2005) [Pubmed]
  3. IL-7 inhibits fibroblast TGF-beta production and signaling in pulmonary fibrosis. Huang, M., Sharma, S., Zhu, L.X., Keane, M.P., Luo, J., Zhang, L., Burdick, M.D., Lin, Y.Q., Dohadwala, M., Gardner, B., Batra, R.K., Strieter, R.M., Dubinett, S.M. J. Clin. Invest. (2002) [Pubmed]
  4. Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. Weitzmann, M.N., Roggia, C., Toraldo, G., Weitzmann, L., Pacifici, R. J. Clin. Invest. (2002) [Pubmed]
  5. Appearance of immature/transitional B cells in HIV-infected individuals with advanced disease: correlation with increased IL-7. Malaspina, A., Moir, S., Ho, J., Wang, W., Howell, M.L., O'Shea, M.A., Roby, G.A., Rehm, C.A., Mican, J.M., Chun, T.W., Fauci, A.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. T cell subsets and their lymphokines. De Berardinis, P. Ann. Ist. Super. Sanita (1991) [Pubmed]
  7. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Ma, A., Koka, R., Burkett, P. Annu. Rev. Immunol. (2006) [Pubmed]
  8. Control of T cell viability. Marrack, P., Kappler, J. Annu. Rev. Immunol. (2004) [Pubmed]
  9. Early T lymphocyte progenitors. Shortman, K., Wu, L. Annu. Rev. Immunol. (1996) [Pubmed]
  10. IL-12-Programmed Long-Term CD8+ T Cell Responses Require STAT4. Li, Q., Eppolito, C., Odunsi, K., Shrikant, P.A. J. Immunol. (2006) [Pubmed]
  11. Jak3 activation in human lymphocyte precursor cells. Sharfe, N., Dadi, H.K., O'Shea, J.J., Roifman, C.M. Clin. Exp. Immunol. (1997) [Pubmed]
  12. Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Adolfsson, J., Månsson, R., Buza-Vidas, N., Hultquist, A., Liuba, K., Jensen, C.T., Bryder, D., Yang, L., Borge, O.J., Thoren, L.A., Anderson, K., Sitnicka, E., Sasaki, Y., Sigvardsson, M., Jacobsen, S.E. Cell (2005) [Pubmed]
  13. Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice. Akashi, K., Kondo, M., von Freeden-Jeffry, U., Murray, R., Weissman, I.L. Cell (1997) [Pubmed]
  14. Cytokine regulation of neuronal differentiation of hippocampal progenitor cells. Mehler, M.F., Rozental, R., Dougherty, M., Spray, D.C., Kessler, J.A. Nature (1993) [Pubmed]
  15. Resident bone marrow macrophages produce type 1 interferons that can selectively inhibit interleukin-7-driven growth of B lineage cells. Wang, J., Lin, Q., Langston, H., Cooper, M.D. Immunity (1995) [Pubmed]
  16. Molecular characterization, reactivation, and depletion of latent HIV. Brooks, D.G., Hamer, D.H., Arlen, P.A., Gao, L., Bristol, G., Kitchen, C.M., Berger, E.A., Zack, J.A. Immunity (2003) [Pubmed]
  17. Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4. Schilham, M.W., Oosterwegel, M.A., Moerer, P., Ya, J., de Boer, P.A., van de Wetering, M., Verbeek, S., Lamers, W.H., Kruisbeek, A.M., Cumano, A., Clevers, H. Nature (1996) [Pubmed]
  18. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Lin, H., Grosschedl, R. Nature (1995) [Pubmed]
  19. Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus. Nutt, S.L., Urbánek, P., Rolink, A., Busslinger, M. Genes Dev. (1997) [Pubmed]
  20. WECHE: a novel hematopoietic regulatory factor. Ohneda, O., Ohneda, K., Nomiyama, H., Zheng, Z., Gold, S.A., Arai, F., Miyamoto, T., Taillon, B.E., McIndoe, R.A., Shimkets, R.A., Lewin, D.A., Suda, T., Lasky, L.A. Immunity (2000) [Pubmed]
  21. Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice. Kondo, M., Akashi, K., Domen, J., Sugamura, K., Weissman, I.L. Immunity (1997) [Pubmed]
  22. An IL-7-dependent rebound in thymic T cell output contributes to the bone loss induced by estrogen deficiency. Ryan, M.R., Shepherd, R., Leavey, J.K., Gao, Y., Grassi, F., Schnell, F.J., Qian, W.P., Kersh, G.J., Weitzmann, M.N., Pacifici, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  23. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Williams, R.T., Roussel, M.F., Sherr, C.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  24. Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein. Iwata, M., Graf, L., Awaya, N., Torok-Storb, B. Blood (2002) [Pubmed]
  25. Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia. Karawajew, L., Ruppert, V., Wuchter, C., Kösser, A., Schrappe, M., Dörken, B., Ludwig, W.D. Blood (2000) [Pubmed]
  26. Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation. Morrissey, P.J., Conlon, P., Braddy, S., Williams, D.E., Namen, A.E., Mochizuki, D.Y. J. Immunol. (1991) [Pubmed]
  27. Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. Miyazaki, T., Kawahara, A., Fujii, H., Nakagawa, Y., Minami, Y., Liu, Z.J., Oishi, I., Silvennoinen, O., Witthuhn, B.A., Ihle, J.N. Science (1994) [Pubmed]
  28. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Khaled, A.R., Li, W.Q., Huang, J., Fry, T.J., Khaled, A.S., Mackall, C.L., Muegge, K., Young, H.A., Durum, S.K. Immunity (2002) [Pubmed]
  29. Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: stat6 is probably not required for the effect of IL-4. Vella, A., Teague, T.K., Ihle, J., Kappler, J., Marrack, P. J. Exp. Med. (1997) [Pubmed]
  30. Shared gamma(c) subunit within the human interleukin-7 receptor complex. A molecular basis for the pathogenesis of X-linked severe combined immunodeficiency. Lai, S.Y., Molden, J., Goldsmith, M.A. J. Clin. Invest. (1997) [Pubmed]
  31. The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Sugamura, K., Asao, H., Kondo, M., Tanaka, N., Ishii, N., Ohbo, K., Nakamura, M., Takeshita, T. Annu. Rev. Immunol. (1996) [Pubmed]
  32. Neonates support lymphopenia-induced proliferation. Min, B., McHugh, R., Sempowski, G.D., Mackall, C., Foucras, G., Paul, W.E. Immunity (2003) [Pubmed]
  33. Mobilization of long-term reconstituting hematopoietic stem cells in mice by recombinant human interleukin 7. Grzegorzewski, K.J., Komschlies, K.L., Jacobsen, S.E., Ruscetti, F.W., Keller, J.R., Wiltrout, R.H. J. Exp. Med. (1995) [Pubmed]
  34. Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. Watanabe, M., Ueno, Y., Yajima, T., Iwao, Y., Tsuchiya, M., Ishikawa, H., Aiso, S., Hibi, T., Ishii, H. J. Clin. Invest. (1995) [Pubmed]
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