Genomes and Genes
Gene Symbol: Il7
Description: interleukin 7
Alias: A630026I06Rik, Il-7, hlb368, interleukin-7
- Ranson T, Vosshenrich C, Corcuff E, Richard O, Muller W, Di Santo J. IL-15 is an essential mediator of peripheral NK-cell homeostasis. Blood. 2003;101:4887-93 pubmed..Using an adoptive transfer system, we have investigated the role of gammac-dependent cytokines, in particular interleukin 7 (IL-7) and IL-15, and major histocompatibility complex (MHC) class I molecules in peripheral NK-cell ..
- Vosshenrich C, Ranson T, Samson S, Corcuff E, Colucci F, Rosmaraki E, et al. Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J Immunol. 2005;174:1213-21 pubmed..Surprisingly, the few residual NK cells generated in absence of IL-15 appear relatively mature, expressing a variety of Ly49 receptors and demonstrating lytic and cytokine production capacity. ..
- Haks M, Oosterwegel M, Blom B, Spits H, Kruisbeek A. Cell-fate decisions in early T cell development: regulation by cytokine receptors and the pre-TCR. Semin Immunol. 1999;11:23-37 pubmed
- 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. ..
- Satoh Takayama N, Lesjean Pottier S, Vieira P, Sawa S, Eberl G, Vosshenrich C, et al. IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors. J Exp Med. 2010;207:273-80 pubmed publisher..1(-)Rorc(+) cells are not canonical NK cell precursors. These studies highlight the independent cytokine regulation of functionally diverse intestinal NKp46(+) cell subsets...
- Seet C, Brumbaugh R, Kee B. Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J Exp Med. 2004;199:1689-700 pubmed..Remarkably, however, we find that E2A proteins are required for interleukin 7-dependent proliferation due, in part, to a role for E2A in optimal expression of N-myc...
- Vosshenrich C, Garcia Ojeda M, Samson Villéger 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 ..
- von Freeden Jeffry U, Solvason N, Howard M, Murray R. The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity. 1997;7:147-54 pubmed..These data specify a T cell lineage developmental transition point, prior to T cell antigen receptor rearrangement, where IL-7 signal transduction is linked to an anti-apoptosis mechanism and the cell cycle. ..
- Murray A, Simm B, Beagley K. Cytokine gene expression in murine fetal intestine: potential for extrathymic T cell development. Cytokine. 1998;10:337-45 pubmed..Stem cell factor (SCF) and interleukin 7 (IL-7) message was abundant in all three tissues during fetal development...
- Sawa S, Kamimura D, Jin G, Morikawa H, Kamon H, Nishihara M, et al. Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells. J Exp Med. 2006;203:1459-70 pubmed
- Weitzmann M, Roggia C, Toraldo G, Weitzmann L, Pacifici R. Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency. J Clin Invest. 2002;110:1643-50 pubmed..Thus, because it targets both the osteoclast and the osteoblast pathways, IL-7 is central to the altered bone turnover characteristic of estrogen deficiency. ..
- El Kassar N, Lucas P, Klug D, Zamisch M, Merchant M, Bare C, et al. A dose effect of IL-7 on thymocyte development. Blood. 2004;104:1419-27 pubmed..These results show for the first time in vivo a dose effect of IL-7 on alphabeta T-cell development and have implications for IL-7 in the clinical setting. ..
- Tan J, Ernst B, Kieper W, LeRoy E, Sprent J, Surh C. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med. 2002;195:1523-32 pubmed..Thus, the homeostatic proliferation mechanisms that control memory CD8+ cells and memory CD4+ cells are quite distinct. ..
- Goldrath A, Sivakumar P, Glaccum M, Kennedy M, Bevan M, Benoist C, et al. Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med. 2002;195:1515-22 pubmed..Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments. ..
- 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
- 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. ..
- Baccala R, Witherden D, Gonzalez Quintial R, Dummer W, Surh C, Havran W, et al. Gamma delta T cell homeostasis is controlled by IL-7 and IL-15 together with subset-specific factors. J Immunol. 2005;174:4606-12 pubmed..Thus, gamma delta T cell homeostasis is maintained by trophic cytokines commonly used by other types of lymphoid cells, as well as by additional, as yet unidentified, gamma delta-specific factors. ..
- Boyman O, Ramsey C, Kim D, Sprent J, Surh C. IL-7/anti-IL-7 mAb complexes restore T cell development and induce homeostatic T Cell expansion without lymphopenia. J Immunol. 2008;180:7265-75 pubmed..The strong stimulatory activity of IL-7/mAb complexes could be useful for treatment of immunodeficiency and cancer. ..
- Wei C, Zeff R, Goldschneider I. Murine pro-B cells require IL-7 and its receptor complex to up-regulate IL-7R alpha, terminal deoxynucleotidyltransferase, and c mu expression. J Immunol. 2000;164:1961-70 pubmed..These key events, in turn, appear to be prerequisite both for differentiation of pro-B cells to pre-B cells and for proliferation of these cell subsets upon continued stimulation with IL-7. ..
- Lenz D, Kurz S, Lemmens E, Schoenberger S, Sprent J, Oldstone M, et al. IL-7 regulates basal homeostatic proliferation of antiviral CD4+T cell memory. Proc Natl Acad Sci U S A. 2004;101:9357-62 pubmed..We propose that homeostatic control of antiviral CD4(+) and CD8(+) T cell memory is fundamentally similar and characterized by quantitative, rather than qualitative, differences. ..
- Peffault De Latour R, Dujardin H, Mishellany F, Burlen Defranoux O, Zuber J, Marques R, et al. Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7. Blood. 2006;108:2300-6 pubmed..It also highlights the potential of the regulatory Foxp3-expressing CD4+CD25- T-cell population to restore a functional CD4+CD25+ T-cell compartment through an IL-7-independent pathway. ..
- Egawa T, Kawabata K, Kawamoto H, Amada K, Okamoto R, Fujii N, et al. The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity. 2001;15:323-34 pubmed..Moreover, SDF-1 exhibited specific biologic activities on the earliest B cell precursors. SDF-1 provides the first example of a cytokine responsible for the earliest B lineage stages. ..
- Venkitaraman A, Cowling R. Interleukin-7 induces the association of phosphatidylinositol 3-kinase with the alpha chain of the interleukin-7 receptor. Eur J Immunol. 1994;24:2168-74 pubmed..PtdIns 3-kinase may, therefore, play a unique and important role in the biological response to IL-7. ..
- Stephan R, Reilly C, Witte P. Impaired ability of bone marrow stromal cells to support B-lymphopoiesis with age. Blood. 1998;91:75-88 pubmed..Therefore, we conclude that the age-related decrease in the function of bone marrow stromal cells is related to the impaired release of IL-7. ..
- Zamisch M, Moore Scott B, Su D, Lucas P, Manley N, Richie E. Ontogeny and regulation of IL-7-expressing thymic epithelial cells. J Immunol. 2005;174:60-7 pubmed
- 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. ..
- Li W, Guszczynski T, Hixon J, Durum S. Interleukin-7 regulates Bim proapoptotic activity in peripheral T-cell survival. Mol Cell Biol. 2010;30:590-600 pubmed publisher..Our findings suggest that the maintenance of peripheral T cells by IL-7 occurs partly through inhibition of Bim activity at the posttranslational level. ..
- Tsuda S, Rieke S, Hashimoto Y, Nakauchi H, Takahama Y. Il-7 supports D-J but not V-DJ rearrangement of TCR-beta gene in fetal liver progenitor cells. J Immunol. 1996;156:3233-42 pubmed
- Kasper L, Matsuura T, Khan I. IL-7 stimulates protective immunity in mice against the intracellular pathogen, Toxoplasma gondii. J Immunol. 1995;155:4798-804 pubmed..These observations indicate that exogenous administration of human rIL-7 is able to protect mice against acute parasite challenge by stimulating IFN-gamma production and augmenting the CD8+ T cell-mediated CTL response. ..
- Watanabe M, Ueno Y, Yajima T, Okamoto S, Hayashi T, Yamazaki M, et al. Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. J Exp Med. 1998;187:389-402 pubmedWe have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor...
- Candeias S, Peschon J, Muegge K, Durum S. Defective T-cell receptor gamma gene rearrangement in interleukin-7 receptor knockout mice. Immunol Lett. 1997;57:9-14 pubmed..These findings indicate that one or both of the two known ligands of IL-7R, IL-7 and thymic stromal lymphopoietin (TSLP) serves as an extrinsic signal to specifically rearrange the TCR gamma locus. ..
- 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. ..
- Miller J, Izon D, DeMuth W, Gerstein R, Bhandoola A, Allman D. The earliest step in B lineage differentiation from common lymphoid progenitors is critically dependent upon interleukin 7. J Exp Med. 2002;196:705-11 pubmed..These findings challenge previous notions regarding the point in B cell development affected by the loss of IL-7R signaling and suggest that IL-7 plays a key and requisite role during the earliest phases of B cell development. ..
- Rathmell J, Farkash E, Gao W, Thompson C. IL-7 enhances the survival and maintains the size of naive T cells. J Immunol. 2001;167:6869-76 pubmed..These data demonstrate that T cells require the continuous presence of extrinsic signals not only to survive but also to maintain their size, metabolic activity, and the ability to respond rapidly to mitogenic signals. ..
- Laky K, Lefrancois L, von Freeden Jeffry U, Murray R, Puddington L. The role of IL-7 in thymic and extrathymic development of TCR gamma delta cells. J Immunol. 1998;161:707-13 pubmed..Thus, intrathymic IL-7 was required for development of thymic TCR gamma delta cells, while peripheral IL-7 was sufficient for development of extrathymic TCR gamma delta IEL. ..
- Winkler T, Melchers F, Rolink A. Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse. Blood. 1995;85:2045-51 pubmed..Thus, IL-7 and IL-3 are alternative growth factors for the same pre-BI cell. ..
- Montgomery R, Dallman M. Semi-quantitative polymerase chain reaction analysis of cytokine and cytokine receptor gene expression during thymic ontogeny. Cytokine. 1997;9:717-26 pubmed..The mRNA abundance and pattern of expression of each cytokine or cytokine receptor may indicate the relative contribution that it makes to different stages of fetal thymic ontogeny. ..
- 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 publisherSTAT5 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...
- Park J, Yu Q, Erman B, Appelbaum J, Montoya Durango D, Grimes H, et al. Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity. 2004;21:289-302 pubmed..We suggest that this homeostatic regulatory mechanism promotes survival of the maximum possible number of T cells for the amount of IL-7 available. ..
- Chowdhury D, Sen R. Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements. Immunity. 2003;18:229-41 pubmed..Thus, transient signals mediate V(H) gene activation and inactivation during development. ..
- Tomita T, Kanai T, Nemoto Y, Totsuka T, Okamoto R, Tsuchiya K, et al. Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis. J Immunol. 2008;180:383-90 pubmed
- Tan J, Dudl E, Leroy E, Murray R, Sprent J, Weinberg K, et al. IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A. 2001;98:8732-7 pubmed..Thus, naïve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7(-) hosts. These findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation. ..
- Mertsching E, Burdet C, Ceredig R. IL-7 transgenic mice: analysis of the role of IL-7 in the differentiation of thymocytes in vivo and in vitro. Int Immunol. 1995;7:401-14 pubmed..We conclude that IL-7 is probably not an important differentiation factor for immature mouse thymocytes. ..
- Kieper W, Burghardt J, Surh C. A role for TCR affinity in regulating naive T cell homeostasis. J Immunol. 2004;172:40-4 pubmed..The results suggest that the strength of the TCR affinity determines the relative "fitness" of naive T cells to compete for factors that support cell survival and homeostatic proliferation. ..
- Buentke E, Mathiot A, Tolaini M, Di Santo J, Zamoyska R, Seddon B. Do CD8 effector cells need IL-7R expression to become resting memory cells?. Blood. 2006;108:1949-56 pubmed
- Lu L, Chaudhury P, Osmond D. Regulation of cell survival during B lymphopoiesis: apoptosis and Bcl-2/Bax content of precursor B cells in bone marrow of mice with altered expression of IL-7 and recombinase-activating gene-2. J Immunol. 1999;162:1931-40 pubmed..The results demonstrate that IL-7 strongly promotes in vivo cell survival and maintains antiapoptotic Bcl-2/Bax ratios during the development of precursor B cells in mouse bone marrow. ..
- Totsuka T, Kanai T, Nemoto Y, Makita S, Okamoto R, Tsuchiya K, et al. IL-7 Is essential for the development and the persistence of chronic colitis. J Immunol. 2007;178:4737-48 pubmed
- Park J, Adoro S, Lucas P, Sarafova S, Alag A, Doan L, et al. 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR. Nat Immunol. 2007;8:1049-59 pubmed..Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR ..
- 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 publisherb>Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation...
- Montgomery R, Dallman M. Analysis of cytokine gene expression during fetal thymic ontogeny using the polymerase chain reaction. J Immunol. 1991;147:554-60 pubmed
- Seddon B, Tomlinson P, Zamoyska R. Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat Immunol. 2003;4:680-6 pubmed..We have shown here that interleukin 7 (IL-7) was an important survival factor for CD4 memory T cells that together with T cell receptor (TCR) ..
- Jin J, Goldschneider I, Lai L. In vivo administration of the recombinant IL-7/hepatocyte growth factor ? hybrid cytokine efficiently restores thymopoiesis and naive T cell generation in lethally irradiated mice after syngeneic bone marrow transplantation. J Immunol. 2011;186:1915-22 pubmed publisher..It also supports the maturation and homeostatic expansion of peripheral T cells. Consequently, the in vivo administration of rIL-7/HGF? may offer a new approach to preventing and/or correcting post-BMT T cell immune deficiency. ..
- Williams I, Rawson E, Manning L, Karaoli T, Rich B, Kupper T. IL-7 overexpression in transgenic mouse keratinocytes causes a lymphoproliferative skin disease dominated by intermediate TCR cells: evidence for a hierarchy in IL-7 responsiveness among cutaneous T cells. J Immunol. 1997;159:3044-56 pubmed..Our results also suggest that features of the epidermal microenvironment besides keratinocyte-derived IL-7 account for the normal predominance of Vgamma5 Vdelta1 DETC in mouse epidermis. ..
- Unsinger J, McGlynn M, Kasten K, Hoekzema A, Watanabe E, Muenzer J, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis. J Immunol. 2010;184:3768-79 pubmed publisher..If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis. ..
- Khaled A, Li W, Huang J, Fry T, Khaled A, Mackall C, et al. Bax deficiency partially corrects interleukin-7 receptor alpha deficiency. Immunity. 2002;17:561-73 pubmed..The BH3 only proteins, Bad and Bim, were also part of the death pathway repressed by IL-7. Thus, in young mice, Bax emerges as an essential protein in the death pathway induced by IL-7 deficiency. ..
- Carvalho T, Mota Santos T, Cumano A, Demengeot J, Vieira P. Arrested B lymphopoiesis and persistence of activated B cells in adult interleukin 7(-/)- mice. J Exp Med. 2001;194:1141-50 pubmedb>Interleukin 7 is a crucial factor for the development of murine T and B lymphocytes...
- Schluns K, Kieper W, Jameson S, Lefrancois L. Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat Immunol. 2000;1:426-32 pubmed..Homeostatic proliferation of memory cells was also partially dependent on IL-7. These results point to IL-7 as a pivotal cytokine in T cell homeostasis. ..
- Namen A, Lupton S, Hjerrild K, Wignall J, Mochizuki D, Schmierer A, et al. Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature. 1988;333:571-3 pubmed..Using direct expression in mammalian cells we have isolated a complementary DNA clone encoding this novel haematopoietic growth factor, designated interleukin-7. ..
- Cho J, Kim H, Surh C, Sprent J. T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell homeostasis. Immunity. 2010;32:214-26 pubmed publisher..Thus, TCR contact with antigen upregulates GM1 and amplifies responsiveness of naive CD8(+) T cells to IL-2, thereby making the cells highly sensitive to exogenous IL-2 from CD4(+) T helper cells. ..
- Allman D, Sambandam A, Kim S, Miller J, Pagan A, Well D, et al. Thymopoiesis independent of common lymphoid progenitors. Nat Immunol. 2003;4:168-74 pubmed..Thymic ETPs were not interleukin 7 (IL-7)-responsive and generated B lineage progeny with delayed kinetics, whereas BM CLPs were IL-7-responsive ..
- Kieper W, Tan J, Bondi Boyd B, Gapin L, Sprent J, Ceredig R, et al. Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells. J Exp Med. 2002;195:1533-9 pubmed..Since these cell are rare in normal IL-15(-) mice, the dependency of memory phenotype CD8+ cells on IL-15 can be overcome by overexpression of IL-7. ..
- Malissen M, Pereira P, Gerber D, Malissen B, DiSanto J. The common cytokine receptor gamma chain controls survival of gamma/delta T cells. J Exp Med. 1997;186:1277-85 pubmed
- Alugupalli K, Gerstein R, Chen J, Szomolanyi Tsuda E, Woodland R, Leong J. The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes. J Immunol. 2003;170:3819-27 pubmed..hermsii. Together these results support the model that B1b cells generate the T-independent IgM required for the control and resolution of relapsing fever borreliosis. ..
- Toraldo G, Roggia C, Qian W, Pacifici R, Weitzmann M. IL-7 induces bone loss in vivo by induction of receptor activator of nuclear factor kappa B ligand and tumor necrosis factor alpha from T cells. Proc Natl Acad Sci U S A. 2003;100:125-30 pubmed..Importantly, T cell adoptive transfer into nude mice restored IL-7-induced bone loss, and RANKL and TNF-alpha secretion, demonstrating that T cells are essential mediators of IL-7-induced bone loss in vivo. ..
- Vonarbourg C, Mortha A, Bui V, Hernandez P, Kiss E, Hoyler T, et al. Regulated expression of nuclear receptor ROR?t confers distinct functional fates to NK cell receptor-expressing ROR?t(+) innate lymphocytes. Immunity. 2010;33:736-51 pubmed publisher..Our data also define a previously unappreciated role of ROR?t? NKR-LTi cells for the onset or maintenance of inflammatory bowel diseases...