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Gene Review

IL7R  -  interleukin 7 receptor

Homo sapiens

Synonyms: CD127, CDW127, CDw127, IL-7 receptor subunit alpha, IL-7R subunit alpha, ...
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Disease relevance of IL7R


High impact information on IL7R


Chemical compound and disease context of IL7R


Biological context of IL7R

  • The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test) [12].
  • These results suggest that PI-3 kinase is involved in signal transduction via the IL-7R in human thymocytes [13].
  • However, the exact mechanism whereby the IL-7 receptor (IL-7R) mediates these cell growth signals remains unknown [13].
  • In response to IL-7 stimulation, Jak-3 phosphorylation was markedly reduced in both patient cells as well as in COS cells reconstituted with mutant IL-7R alpha [14].
  • These results indicate that IL-7R alpha expression defines entry into a developmental stage characterized by upregulation of multiple lymphoid-associated genes and enhanced fitness for B-lymphoid differentiation [15].

Anatomical context of IL7R


Associations of IL7R with chemical compounds

  • These data suggest that IL-7 may function to regulate the milieu of the microenvironment by modulating IL-6 secretion by the IL-7R-expressing stromal elements [16].
  • Substitution of proline with serine in the extracellular portion of IL-7R alpha did not affect IL-7R alpha messenger RNA (mRNA) and protein expression, but severely compromised affinity to IL-7, resulting in defective signal transduction [14].
  • The effects of IL-7 and cycloheximide on IL-7R expression by peripheral blood mononuclear cells were examined in vitro [2].
  • In this study we describe abrogation of IL-7 driven proliferation and attenuated phosphotyrosine signaling by IL-7(143) (Trp-Ala) and IL-7(143) (Trp-His) in IL-7R expressing T and B leukemia cells [18].
  • Alteration of a single tyrosine residue, Tyr410, in the IL-7R cytoplasmic domain to phenylalanine also prevents the inhibition of proliferation after antigen receptor assembly [19].

Physical interactions of IL7R


Regulatory relationships of IL7R

  • IL-7R alpha-expressing but not parental 32D cells proliferate in the presence of exogenous TSLP [21].
  • Incubation of all seven patients' cells with IL7 induced coexpression to varying degrees of IL7-R and IL2-R [22].
  • It is likely that higher TGF-beta concentrations do not inhibit lymphopoiesis by down-regulating IL-7 receptor expression, since this cytokine did not reduce IL-7R alpha or gamma c mRNA levels in normal B cell precursors [23].
  • Compared to Flu, VV or EBV, HIV tetramer+ CD8 T cells expressed significantly lower levels of CD127, and this reduction was pervasive across all epitopes and alleles tested and over a wide range of viral loads and CD4 counts [24].

Other interactions of IL7R

  • Untreated viremic patients showed a slight but significant decrease in CD127 expression on the surface of their CD4 lymphocytes [25].
  • By contrast, CD127 expression was substantially altered on the surface of CD8 T lymphocytes taken from untreated viremic patients [25].
  • Decreased phosphorylation of Jak3 kinase by IL-7W143A, IL-7W143P and IL-7W143H suggest that alterations in this region of the carboxyterminal region of IL-7 affects its interaction with the gammac subunit of the IL-7R [18].
  • Surprisingly, in a substantial part of the myeloid lineage cells examined, an IL-2Rgamma+, IL-4R-, IL7R- configuration was noted that was, however, frequently associated with expression of IL-9R [26].
  • Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and the IL-7R alpha-chain [27].

Analytical, diagnostic and therapeutic context of IL7R


  1. Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Puel, A., Ziegler, S.F., Buckley, R.H., Leonard, W.J. Nat. Genet. (1998) [Pubmed]
  2. Increased plasma interleukin-7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection. Sasson, S.C., Zaunders, J.J., Zanetti, G., King, E.M., Merlin, K.M., Smith, D.E., Stanley, K.K., Cooper, D.A., Kelleher, A.D. J. Infect. Dis. (2006) [Pubmed]
  3. Bacterial invasion induces interleukin-7 receptor expression in colonic epithelial cell line, T84. Yamada, K., Shimaoka, M., Nagayama, K., Hiroi, T., Kiyono, H., Honda, T. Eur. J. Immunol. (1997) [Pubmed]
  4. Dysregulation of interleukin-7 receptor may generate loss of cytotoxic T cell response in human immunodeficiency virus type 1 infection. Carini, C., McLane, M.F., Mayer, K.H., Essex, M. Eur. J. Immunol. (1994) [Pubmed]
  5. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Gregory, S.G., Schmidt, S., Seth, P., Oksenberg, J.R., Hart, J., Prokop, A., Caillier, S.J., Ban, M., Goris, A., Barcellos, L.F., Lincoln, R., McCauley, J.L., Sawcer, S.J., Compston, D.A., Dubois, B., Hauser, S.L., Garcia-Blanco, M.A., Pericak-Vance, M.A., Haines, J.L. Nat. Genet. (2007) [Pubmed]
  6. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Goodwin, R.G., Friend, D., Ziegler, S.F., Jerzy, R., Falk, B.A., Gimpel, S., Cosman, D., Dower, S.K., March, C.J., Namen, A.E. Cell (1990) [Pubmed]
  7. Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Corcoran, A.E., Riddell, A., Krooshoop, D., Venkitaraman, A.R. Nature (1998) [Pubmed]
  8. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Noguchi, M., Nakamura, Y., Russell, S.M., Ziegler, S.F., Tsang, M., Cao, X., Leonard, W.J. Science (1993) [Pubmed]
  9. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Russell, S.M., Keegan, A.D., Harada, N., Nakamura, Y., Noguchi, M., Leland, P., Friedmann, M.C., Miyajima, A., Puri, R.K., Paul, W.E. Science (1993) [Pubmed]
  10. Combined immunodeficiencies due to defects in signal transduction: defects of the gammac-JAK3 signaling pathway as a model. Notarangelo, L.D., Giliani, S., Mella, P., Schumacher, R.F., Mazza, C., Savoldi, G., Rodriguez-Pérez, C., Badolato, R., Mazzolari, E., Porta, F., Candotti, F., Ugazio, A.G. Immunobiology (2000) [Pubmed]
  11. Engagement of interleukin-7 receptor stimulates tyrosine phosphorylation, phosphoinositide turnover, and clonal proliferation of human T-lineage acute lymphoblastic leukemia cells. Dibirdik, I., Langlie, M.C., Ledbetter, J.A., Tuel-Ahlgren, L., Obuz, V., Waddick, K.G., Gajl-Peczalska, K., Schieven, G.L., Uckun, F.M. Blood (1991) [Pubmed]
  12. Gene expression and genotyping studies implicate the interleukin 7 receptor in the pathogenesis of primary progressive multiple sclerosis. Booth, D.R., Arthur, A.T., Teutsch, S.M., Bye, C., Rubio, J., Armati, P.J., Pollard, J.D., Heard, R.N., Stewart, G.J. J. Mol. Med. (2005) [Pubmed]
  13. Activation of phosphatidylinositol-3 kinase by ligation of the interleukin-7 receptor on human thymocytes. Dadi, H.K., Roifman, C.M. J. Clin. Invest. (1993) [Pubmed]
  14. A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency. Roifman, C.M., Zhang, J., Chitayat, D., Sharfe, N. Blood (2000) [Pubmed]
  15. Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity. Ryan, D.H., Nuccie, B.L., Ritterman, I., Liesveld, J.L., Abboud, C.N., Insel, R.A. Blood (1997) [Pubmed]
  16. 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]
  17. Role of interleukin-7 in T-cell development from hematopoietic stem cells. Akashi, K., Kondo, M., Weissman, I.L. Immunol. Rev. (1998) [Pubmed]
  18. Altered biological activity associated with C-terminal modifications of IL-7. Görgün, G., van der Spek, J., Cosenza, L., Menevse, A., Foss, F. Cytokine (2002) [Pubmed]
  19. Inhibition of interleukin 7 receptor signaling by antigen receptor assembly. Smart, F.M., Venkitaraman, A.R. J. Exp. Med. (2000) [Pubmed]
  20. IL-7 receptor is present on human microvascular endothelial cells. Duś, D., Krawczenko, A., Załecki, P., Paprocka, M., Wiedłocha, A., Goupille, C., Kieda, C. Immunol. Lett. (2003) [Pubmed]
  21. Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Pandey, A., Ozaki, K., Baumann, H., Levin, S.D., Puel, A., Farr, A.G., Ziegler, S.F., Leonard, W.J., Lodish, H.F. Nat. Immunol. (2000) [Pubmed]
  22. Costimulation of cutaneous T-cell lymphoma cells by interleukin-7 and interleukin-2: potential autocrine or paracrine effectors in the Sézary syndrome. Foss, F.M., Koc, Y., Stetler-Stevenson, M.A., Nguyen, D.T., O'Brien, M.C., Turner, R., Sausville, E.A. J. Clin. Oncol. (1994) [Pubmed]
  23. TGF-beta down-regulates stromal IL-7 secretion and inhibits proliferation of human B cell precursors. Tang, J., Nuccie, B.L., Ritterman, I., Liesveld, J.L., Abboud, C.N., Ryan, D.H. J. Immunol. (1997) [Pubmed]
  24. HIV-specific CD8 T cells express low levels of IL-7Ralpha: Implications for HIV-specific T cell memory. Wherry, E.J., Day, C.L., Draenert, R., Miller, J.D., Kiepiela, P., Woodberry, T., Brander, C., Addo, M., Klenerman, P., Ahmed, R., Walker, B.D. Virology (2006) [Pubmed]
  25. Regulatory dysfunction of the interleukin-7 receptor in CD4 and CD8 lymphocytes from HIV-infected patients--effects of antiretroviral therapy. Colle, J.H., Moreau, J.L., Fontanet, A., Lambotte, O., Joussemet, M., Jacod, S., Delfraissy, J.F., Thèze, J. J. Acquir. Immune Defic. Syndr. (2006) [Pubmed]
  26. Transcript synthesis and surface expression of the interleukin-2 receptor (alpha-, beta-, and gamma-chain) by normal and malignant myeloid cells. Schumann, R.R., Nakarai, T., Gruss, H.J., Brach, M.A., von Arnim, U., Kirschning, C., Karawajew, L., Ludwig, W.D., Renauld, J.C., Ritz, J., Herrmann, F. Blood (1996) [Pubmed]
  27. Human thymic stromal lymphopoietin preferentially stimulates myeloid cells. Reche, P.A., Soumelis, V., Gorman, D.M., Clifford, T., Liu Mr, n.u.l.l., Travis, M., Zurawski, S.M., Johnston, J., Liu, Y.J., Spits, H., de Waal Malefyt, R., Kastelein, R.A., Bazan, J.F. J. Immunol. (2001) [Pubmed]
  28. Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life. Nasi, M., Troiano, L., Lugli, E., Pinti, M., Ferraresi, R., Monterastelli, E., Mussi, C., Salvioli, G., Franceschi, C., Cossarizza, A. Aging Cell (2006) [Pubmed]
  29. IL-7/IL-7 receptor system regulation following IL-2 immunotherapy in HIV-infected patients. Marchetti, G., Meroni, L., Molteni, C., Taskaris, G., Gazzola, L., Galli, M., Clerici, M., Moroni, M., Franzetti, F., Gori, A. Antivir. Ther. (Lond.) (2004) [Pubmed]
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