interleukin 7


Summary: A cytokine produced by bone marrow stromal cells that promotes the growth of B-LYMPHOCYTE precursors and is co-mitogenic with INTERLEUKIN-2 for mature T-LYMPHOCYTE activation.

Top Publications

  1. van Amelsfort J, van Roon J, Noordegraaf M, Jacobs K, Bijlsma J, Lafeber F, et al. Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum. 2007;56:732-42 pubmed
  2. Vassena L, Proschan M, Fauci A, Lusso P. Interleukin 7 reduces the levels of spontaneous apoptosis in CD4+ and CD8+ T cells from HIV-1-infected individuals. Proc Natl Acad Sci U S A. 2007;104:2355-60 pubmed
    ..Here, we show that interleukin 7 (IL-7), a nonredundant cytokine that plays essential roles in the generation and homeostasis of the T cell ..
  3. Guimond M, Veenstra R, Grindler D, Zhang H, Cui Y, Murphy R, et al. Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells. Nat Immunol. 2009;10:149-57 pubmed publisher
    b>Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation...
  4. van Roon J, Hartgring S, Wenting van Wijk M, Jacobs K, Tak P, Bijlsma J, et al. Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha blockade in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:664-9 pubmed
  5. Roessler S, Gyory I, Imhof S, Spivakov M, Williams R, Busslinger M, et al. Distinct promoters mediate the regulation of Ebf1 gene expression by interleukin-7 and Pax5. Mol Cell Biol. 2007;27:579-94 pubmed
    ..Taken together, these data suggest that the regulation of Ebf1 via distinct promoters allows for the generation of several feedback loops and the coordination of multiple determinants of B lymphopoiesis in a regulatory network. ..
  6. Hartgring S, Bijlsma J, Lafeber F, van Roon J. Interleukin-7 induced immunopathology in arthritis. Ann Rheum Dis. 2006;65 Suppl 3:iii69-74 pubmed
    ..Together this suggests that IL-7 is an important cytokine in several rheumatic conditions, capable of inducing inflammation and immunopathology. Thus it may be an important target for immunotherapy. ..
  7. Allard E, Hardy M, Leignadier J, Marquis M, Rooney J, Lehoux D, et al. Overexpression of IL-21 promotes massive CD8+ memory T cell accumulation. Eur J Immunol. 2007;37:3069-77 pubmed
    ..This study identifies new roles for IL-21 in T cell homeostasis and in the regulation of T cell responses to cytokines. ..
  8. Colucci S, Brunetti G, Cantatore F, Oranger A, Mori G, Quarta L, et al. Lymphocytes and synovial fluid fibroblasts support osteoclastogenesis through RANKL, TNFalpha, and IL-7 in an in vitro model derived from human psoriatic arthritis. J Pathol. 2007;212:47-55 pubmed
    ..Our results suggest that fibroblasts, B and T lymphocytes support OC formation by producing RANKL, TNFalpha, and IL-7, contributing to the aggressive bone resorption in PsA patients. ..
  9. Malin S, McManus S, Cobaleda C, Novatchkova M, Delogu A, Bouillet P, et al. Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development. Nat Immunol. 2010;11:171-9 pubmed publisher
    STAT5 and interleukin 7 (IL-7) signaling are thought to control B lymphopoiesis by regulating the expression of key transcription factors and by activating variable (V(H)) gene segments at the immunoglobulin heavy-chain (Igh) locus...

More Information


  1. Li B, VanRoey M, Jooss K. Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy. Clin Immunol. 2007;123:155-65 pubmed
    ..Taken together, these studies demonstrate that IL-7 augments the anti-tumor response of a GM-CSF-secreting tumor cell immunotherapy in preclinical models. ..
  2. Mazzucchelli R, Durum S. Interleukin-7 receptor expression: intelligent design. Nat Rev Immunol. 2007;7:144-54 pubmed
  3. Roato I, Brunetti G, Gorassini E, Grano M, Colucci S, Bonello L, et al. IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by solid tumor. PLoS ONE. 2006;1:e124 pubmed
    ..These findings add further details to the disclosure of the mechanisms controlling bone metastasis in solid tumors. ..
  4. Sato N, Patel H, Waldmann T, Tagaya Y. The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells. Proc Natl Acad Sci U S A. 2007;104:588-93 pubmed
  5. Vosshenrich C, Garcia Ojeda M, Samson Vill├ęger S, Pasqualetto V, Enault L, Richard Le Goff O, et al. A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol. 2006;7:1217-24 pubmed
    ..NK cells repopulated peripheral lymphoid organs, and their homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK cells had a distinct phenotype (CD11b(lo) CD16- CD69(hi) Ly49(lo)) and unusual functional ..
  6. Surh C, Boyman O, Purton J, Sprent J. Homeostasis of memory T cells. Immunol Rev. 2006;211:154-63 pubmed
    ..For memory CD4+ T cells, IL-7 has an important role, whereas the influence of IL-15 is still unclear. ..
  7. Fluur C, De Milito A, Fry T, Vivar N, Eidsmo L, Atlas A, et al. Potential role for IL-7 in Fas-mediated T cell apoptosis during HIV infection. J Immunol. 2007;178:5340-50 pubmed
    ..Elevated IL-7 levels associated with lymphopenic conditions, including HIV-infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis. ..
  8. Meier D, Bornmann C, Chappaz S, Schmutz S, Otten L, Ceredig R, et al. Ectopic lymphoid-organ development occurs through interleukin 7-mediated enhanced survival of lymphoid-tissue-inducer cells. Immunity. 2007;26:643-54 pubmed
    ..Therefore, by controlling LTi cell numbers, IL-7 can regulate the formation of both normal and ectopic lymphoid organs. ..
  9. van Lent A, Dontje W, Nagasawa M, Siamari R, Bakker A, Pouw S, et al. IL-7 enhances thymic human T cell development in "human immune system" Rag2-/-IL-2Rgammac-/- mice without affecting peripheral T cell homeostasis. J Immunol. 2009;183:7645-55 pubmed publisher
    ..Overall, our results provide evidence for an important role of IL-7 in human T cell development in vivo and highlight the notion that IL-7 availability is but one of many signals that condition peripheral T cell homeostasis. ..
  10. Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallstrom E, Khademi M, et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet. 2007;39:1108-13 pubmed
    ..Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor alpha chain (IL7Ralpha), indeed contribute to the non-HLA genetic risk in multiple sclerosis, ..
  11. Kim H, Hwang K, Kang I. Dual roles of IL-15 in maintaining IL-7RalphalowCCR7- memory CD8+ T cells in humans via recovering the phosphatidylinositol 3-kinase/AKT pathway. J Immunol. 2007;179:6734-40 pubmed
    ..Moreover, IL-15 can be useful in reviving impaired proliferative function of such memory CD8(+) T cells with effector functions against infections and tumors via rescuing the PI3K/AKT pathway. ..
  12. Pellegrini M, Calzascia T, Elford A, Shahinian A, Lin A, Dissanayake D, et al. Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med. 2009;15:528-36 pubmed publisher
    ..The ability of adjuvant IL-7 to antagonize inhibitory networks at the cellular and molecular level has major implications for immunotherapy in the treatment of tumors. ..
  13. Johnson K, Hashimshony T, Sawai C, Pongubala J, Skok J, Aifantis I, et al. Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity. 2008;28:335-45 pubmed publisher
    ..We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7-expressing stromal cells. ..
  14. Wofford J, Wieman H, Jacobs S, Zhao Y, Rathmell J. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival. Blood. 2008;111:2101-11 pubmed
  15. Rajasuriar R, Booth D, Solomon A, Chua K, Spelman T, Gouillou M, et al. Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor ? and microbial translocation. J Infect Dis. 2010;202:1254-64 pubmed publisher
    ..We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor ? (IL-7R?) gene were important for immune recovery...
  16. Singh H, Pongubala J, Medina K. Gene regulatory networks that orchestrate the development of B lymphocyte precursors. Adv Exp Med Biol. 2007;596:57-62 pubmed
    ..1, Ikaros, E2A, EBF and Pax-5. We review recent experimental evidence concerning the molecular functions of these regulatory components and attempt to connect them in sequentially acting and inter-dependent regulatory modules. ..
  17. Schmutz S, Bosco N, Chappaz S, Boyman O, Acha Orbea H, Ceredig R, et al. Cutting edge: IL-7 regulates the peripheral pool of adult ROR gamma+ lymphoid tissue inducer cells. J Immunol. 2009;183:2217-21 pubmed publisher
    ..Our observations demonstrate that adult CD4(+)lineage(-) cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool. ..
  18. Levy Y, Lacabaratz C, Weiss L, Viard J, Goujard C, Lelievre J, et al. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest. 2009;119:997-1007 pubmed publisher
    ..Therefore, patients may benefit from intermittent therapy with IL-7 in combination with c-ART. ..
  19. Long D, Blake S, Song X, Lark M, Loeser R. Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13. Arthritis Res Ther. 2008;10:R23 pubmed publisher
    ..These novel findings indicate that IL-7 may contribute to cartilage destruction in joint diseases, including osteoarthritis. ..
  20. Lambeck A, Crijns A, Leffers N, Sluiter W, ten Hoor K, Braid M, et al. Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a potential role for interleukin 7. Clin Cancer Res. 2007;13:2385-91 pubmed
    ..IL-7 levels were found to be strongly associated with ovarian cancer and could be used in combination with CA-125 to distinguish between malignant and benign ovarian tumors. ..
  21. Brown V, Hulitt J, Fish J, Sheen C, Bruno M, Xu Q, et al. Thymic stromal-derived lymphopoietin induces proliferation of pre-B leukemia and antagonizes mTOR inhibitors, suggesting a role for interleukin-7Ralpha signaling. Cancer Res. 2007;67:9963-70 pubmed
    ..Thus, further exploration of the IL-7Ralpha pathway may identify potential therapeutic targets in the treatment of ALL. Our data illustrate that growth-factor-mediated signaling may provide one mechanism of MTI resistance. ..
  22. Lundmark F, Duvefelt K, Hillert J. Genetic association analysis of the interleukin 7 gene (IL7) in multiple sclerosis. J Neuroimmunol. 2007;192:171-3 pubmed
    ..We conclude that the IL7 gene is very unlikely to influence the genetic susceptibility to MS in this population. ..
  23. Song H, Nakayama E, Likanonsakul S, Wasi C, Iwamoto A, Shioda T. A three-base-deletion polymorphism in the upstream non-coding region of human interleukin 7 (IL-7) gene could enhance levels of IL-7 expression. Int J Immunogenet. 2007;34:107-13 pubmed
    b>Interleukin 7 (IL-7) is a key factor in the survival, development and proliferation of B and T lymphocytes. Elevation of plasma IL-7 has been reported in several lymphopenia cases such as HIV-1 patients...
  24. Purton J, Tan J, Rubinstein M, Kim D, Sprent J, Surh C. Antiviral CD4+ memory T cells are IL-15 dependent. J Exp Med. 2007;204:951-61 pubmed
    ..Therefore, under normal physiological conditions, homeostasis of CD8(+) and CD4(+) memory cells is quite similar and involves IL-15 and IL-7. ..
  25. Klonowski K, Williams K, Marzo A, Lefrancois L. Cutting edge: IL-7-independent regulation of IL-7 receptor alpha expression and memory CD8 T cell development. J Immunol. 2006;177:4247-51 pubmed
    ..Thus, IL-7Ralpha regulation occurs independently of IL-7 in responding CD8 T cells, indicating that CD8 memory T cell precursors are not selected by IL-7/IL-7Ralpha interactions. ..
  26. Scupoli M, Perbellini O, Krampera M, Vinante F, Cioffi F, Pizzolo G. Interleukin 7 requirement for survival of T-cell acute lymphoblastic leukemia and human thymocytes on bone marrow stroma. Haematologica. 2007;92:264-6 pubmed
    ..We presented evidence that IL-7 has a major role in the enhanced survival mediated by BM stroma both in T-ALL cells and thymocytes. ..
  27. Sereti I, Dunham R, Spritzler J, Aga E, Proschan M, Medvik K, et al. IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood. 2009;113:6304-14 pubmed publisher
    b>Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes...
  28. Sawa Y, Arima Y, Ogura H, Kitabayashi C, Jiang J, Fukushima T, et al. Hepatic interleukin-7 expression regulates T cell responses. Immunity. 2009;30:447-57 pubmed publisher
  29. Ming J, Zhang Q, Qiu X, Wang E. Interleukin 7/interleukin 7 receptor induce c-Fos/c-Jun-dependent vascular endothelial growth factor-D up-regulation: a mechanism of lymphangiogenesis in lung cancer. Eur J Cancer. 2009;45:866-73 pubmed publisher
    b>Interleukin 7 (IL-7) is known to promote lymphangiogenesis...
  30. Nakayama J, Yamamoto M, Hayashi K, Satoh H, Bundo K, Kubo M, et al. BLNK suppresses pre-B-cell leukemogenesis through inhibition of JAK3. Blood. 2009;113:1483-92 pubmed publisher
    ..Thus, somatic loss of BLNK and concomitant mutations leading to constitutive activation of Jak/STAT5 pathway result in the generation of pre-B-cell leukemia. ..
  31. Sportes C, Hakim F, Memon S, Zhang H, Chua K, Brown M, et al. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med. 2008;205:1701-14 pubmed publisher
  32. Bayer A, Lee J, de la Barrera A, Surh C, Malek T. A function for IL-7R for CD4+CD25+Foxp3+ T regulatory cells. J Immunol. 2008;181:225-34 pubmed
    ..Collectively, these data indicate that IL-7R signaling contributes to Treg cell development and peripheral homeostasis. ..
  33. de Lalla C, Festuccia N, Albrecht I, Chang H, Andolfi G, Benninghoff U, et al. Innate-like effector differentiation of human invariant NKT cells driven by IL-7. J Immunol. 2008;180:4415-24 pubmed
    ..The innate nature of human iNKT cells could thus derive from lineage-specific developmental cues that selectively make these cells efficient IL-7 responders following thymic selection. ..
  34. Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood. 2005;106:2472-83 pubmed
  35. Kieper W, Troy A, Burghardt J, Ramsey C, Lee J, Jiang H, et al. Recent immune status determines the source of antigens that drive homeostatic T cell expansion. J Immunol. 2005;174:3158-63 pubmed
    ..Thus, polyclonal naive T cell expansion in T cell-deficient hosts can be driven predominantly by either self-Ags or foreign Ags depending on the host's previous state of T cell immunocompetency. ..
  36. Dias S, Silva H, Cumano A, Vieira P. Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors. J Exp Med. 2005;201:971-9 pubmed
    ..This is the first example of a cytokine influencing lymphoid lineage commitment in multipotent progenitors and highlights the relevance of the expression of a functional IL-7 receptor at the CLP stage. ..
  37. Kikuchi K, Lai A, Hsu C, Kondo M. IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF. J Exp Med. 2005;201:1197-203 pubmed
    ..Thus, IL-7 receptor signaling is a participant in the formation of the transcription factor network during B lymphopoiesis by up-regulating EBF, allowing stage transition from the pre-pro-B to further maturational stages. ..
  38. Melchionda F, Fry T, Milliron M, McKirdy M, Tagaya Y, Mackall C. Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool. J Clin Invest. 2005;115:1177-87 pubmed
  39. Jiang Q, Li W, Aiello F, Mazzucchelli R, Asefa B, Khaled A, et al. Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev. 2005;16:513-33 pubmed
    ..There remain significant questions regarding IL-7 production and the major producing cells have yet to be fully characterized. ..
  40. Rethi B, Fluur C, Atlas A, Krzyzowska M, Mowafi F, Grutzmeier S, et al. Loss of IL-7Ralpha is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients. AIDS. 2005;19:2077-86 pubmed
    ..Differentiation towards a CD28-negative memory phenotype in response to chronic activation may lead to an overall decrease of IL-7 mediated survival within the peripheral T-cell pool. ..
  41. Johnson S, Shah N, Panoskaltsis Mortari A, Lebien T. Murine and human IL-7 activate STAT5 and induce proliferation of normal human pro-B cells. J Immunol. 2005;175:7325-31 pubmed
    ..Our results support a model wherein IL-7 transduces a replicative signal to normal human B-lineage cells that is complemented by additional stromal cell-derived signals essential for normal human B cell development. ..
  42. Milne C, Paige C. IL-7: a key regulator of B lymphopoiesis. Semin Immunol. 2006;18:20-30 pubmed
    ..The production of B cells in IL-7 containing cultures is balanced by cell death, since such cells fail to survive for long without additional stimulation. ..
  43. Kim H, Hong M, Dan J, Kang I. Altered IL-7Ralpha expression with aging and the potential implications of IL-7 therapy on CD8+ T-cell immune responses. Blood. 2006;107:2855-62 pubmed
  44. Harnaha J, Machen J, Wright M, Lakomy R, Styche A, Trucco M, et al. Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells. Diabetes. 2006;55:158-70 pubmed
  45. Krawczenko A, Kieda C, Dus D. The biological role and potential therapeutic application of interleukin 7. Arch Immunol Ther Exp (Warsz). 2005;53:518-25 pubmed
    ..Several therapeutic applications of recombinant IL-7 have been proposed. These have focused on the enhancement of lymphopoiesis, promotion of stem cell engraftment, and the anti-tumor activity of the cytokine. ..
  46. Liu S, Riley J, Rosenberg S, Parkhurst M. Comparison of common gamma-chain cytokines, interleukin-2, interleukin-7, and interleukin-15 for the in vitro generation of human tumor-reactive T lymphocytes for adoptive cell transfer therapy. J Immunother. 2006;29:284-93 pubmed
  47. van Roon J, Verweij M, Wijk M, Jacobs K, Bijlsma J, Lafeber F. Increased intraarticular interleukin-7 in rheumatoid arthritis patients stimulates cell contact-dependent activation of CD4(+) T cells and macrophages. Arthritis Rheum. 2005;52:1700-10 pubmed
    ..Further identification of IL-7-induced pathways may improve understanding of the important interactive role of CD4(+) T cells and monocytic cells in RA. ..
  48. Bertolino E, Reddy K, Medina K, Parganas E, Ihle J, Singh H. Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5. Nat Immunol. 2005;6:836-43 pubmed
    Rearrangement of immunoglobulin heavy-chain variable (V(H)) gene segments has been suggested to be regulated by interleukin 7 signaling in pro-B cells. However, the genetic evidence for this recombination pathway has been challenged...
  49. Khaled A, Bulavin D, Kittipatarin C, Li W, Alvarez M, Kim K, et al. Cytokine-driven cell cycling is mediated through Cdc25A. J Cell Biol. 2005;169:755-63 pubmed
    ..that in lymphocyte cell lines dependent on interleukin-3 or interleukin-7, or primary lymphocytes dependent on interleukin 7, the phosphatase Cdc25A is the critical mediator of proliferation...
  50. Li W, Jiang Q, Aleem E, Kaldis P, Khaled A, Durum S. IL-7 promotes T cell proliferation through destabilization of p27Kip1. J Exp Med. 2006;203:573-82 pubmed
    ..Hence, IL-7 maintains T cell proliferation through a novel pathway of p27Kip1 regulation. ..
  51. Ma A, Koka R, Burkett P. Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol. 2006;24:657-79 pubmed
    ..Trans-presentation also raises several novel cell biological and cellular implications concerning how cytokines support lymphoid homeostasis. ..
  52. Bradley L, Haynes L, Swain S. IL-7: maintaining T-cell memory and achieving homeostasis. Trends Immunol. 2005;26:172-6 pubmed
    ..In this Review, we discuss the role of IL-7 in the survival and homeostasis of naive and memory T cells and how that role is regulated by other factors. ..
  53. Lelievre J, Petit F, Arnoult D, Ameisen J, Estaquier J. Interleukin 7 increases human immunodeficiency virus type 1 LAI-mediated Fas-induced T-cell death. J Virol. 2005;79:3195-9 pubmed
    ..Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4(+) and CD8(+) T-cell death induced by HIV-1(LAI)...