Genomes and Genes
Gene Symbol: Il7r
Description: interleukin 7 receptor
Alias: CD127, IL-7Ralpha, interleukin-7 receptor subunit alpha, IL-7 receptor alpha chain, IL-7 receptor subunit alpha, IL-7R subunit alpha, IL-7R-alpha, IL-7RA, interleukin 7 receptor alpha chain
- Jiang Q, Li W, Hofmeister R, Young H, Hodge D, Keller J, et al. Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members. Mol Cell Biol. 2004;24:6501-13 pubmed..Thus the IL-7 receptor controls at least two distinct pathways, in addition to Stat5, that are required for cell survival. ..
- Erlandsson L, Licence S, Gaspal F, Bell S, Lane P, Corcoran A, et al. Impaired B-1 and B-2 B cell development and atypical splenic B cell structures in IL-7 receptor-deficient mice. Eur J Immunol. 2004;34:3595-603 pubmed..The impairment of marginal zone and B-1 B cells in IL-7 receptor- but not IL-7-deficient mice suggests non-redundant functions for the IL-7 receptor ligands, IL-7 and thymic stromal lymphopoietin. ..
- Porter B, Scibelli P, Malek T. Control of T cell development in vivo by subdomains within the IL-7 receptor alpha-chain cytoplasmic tail. J Immunol. 2001;166:262-9 pubmed..Thus, separate cytoplasmic domains of the IL-7R alpha chain differentially control distinct functions during T cell development, whereas normal IL-7R-dependent thymic development requires the integrated activity of all these domains. ..
- Corcoran A, Riddell A, Krooshoop D, Venkitaraman A. Impaired immunoglobulin gene rearrangement in mice lacking the IL-7 receptor. Nature. 1998;391:904-7 pubmed..This mechanism augments the recombinational diversity of the primary antibody repertoire. ..
- Seddon B, Zamoyska R. TCR and IL-7 receptor signals can operate independently or synergize to promote lymphopenia-induced expansion of naive T cells. J Immunol. 2002;169:3752-9 pubmed..Finally, we show that only lck and not fyn can mediate the TCR-driven proliferation, while neither lck nor fyn is required for IL-7R-induced proliferation. ..
- Serwold T, Ehrlich L, Weissman I. Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis. Blood. 2009;113:807-15 pubmed publisher..These results identify CLPs as the major source of thymocyte progenitors within the BM. ..
- Hamada H, Hiroi T, Nishiyama Y, Takahashi H, Masunaga Y, Hachimura S, et al. Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol. 2002;168:57-64 pubmed..These findings indicate that ILF, PP, and CP constitute three distinct organized gut-associated lymphoid tissues that reside in the lamina propria of the mouse small intestine. ..
- Vosshenrich C, Cumano A, Muller W, Di Santo J, Vieira P. Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development. Nat Immunol. 2003;4:773-9 pubmed..The residual B cells found in IL-7R alpha-deficient mice required fetal liver kinase 2 (Flk-2) for their development. Thus, IL-7R alpha- and Flk-2-mediated signals account for the generation of almost all mouse B lymphocytes. ..
- Schwarz B, Sambandam A, Maillard I, Harman B, Love P, Bhandoola A. Selective thymus settling regulated by cytokine and chemokine receptors. J Immunol. 2007;178:2008-17 pubmed..We conclude that fms-like tyrosine kinase receptor-3 signaling is required for the generation of T lineage-competent progenitors, which selectively express molecules, including CCR9, that allow them to settle within the thymus. ..
- 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..Here we identify the transcription factor GATA-3 and CD127 (IL-7R alpha) as molecular markers of a pathway of mouse NK cell development that originates in the thymus...
- 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
- Maraskovsky E, O Reilly L, Teepe M, Corcoran L, Peschon J, Strasser A. Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice. Cell. 1997;89:1011-9 pubmed..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2. ..
- Shriner A, Liu H, Sun G, Guimond M, Alugupalli K. IL-7-dependent B lymphocytes are essential for the anti-polysaccharide response and protective immunity to Streptococcus pneumoniae. J Immunol. 2010;185:525-31 pubmed publisher..Moreover, immunized young or adult IL-7 transgenic mice were completely resistant to S. pneumoniae challenge. Our data indicate that activating the IL-7 signaling pathway could restore impaired TI responses in the young. ..
- Sitnicka E, Brakebusch C, Martensson I, Svensson M, Agace W, Sigvardsson M, et al. Complementary signaling through flt3 and interleukin-7 receptor alpha is indispensable for fetal and adult B cell genesis. J Exp Med. 2003;198:1495-506 pubmed..Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7Ralpha are indispensable for fetal and adult B cell development. ..
- Yamazaki M, Yajima T, Tanabe M, Fukui K, Okada E, Okamoto R, et al. Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis. J Immunol. 2003;171:1556-63 pubmed
- Peschon J, Morrissey P, Grabstein K, Ramsdell F, Maraskovsky E, Gliniak B, et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med. 1994;180:1955-60 pubmed..Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7. ..
- 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. ..
- Yu Q, Erman B, Park J, Feigenbaum L, Singer A. IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat: impact on thymocyte development. J Exp Med. 2004;200:797-803 pubmed..We conclude that IL-7R signals down-regulate transcription factors required for the ISP to DP transition and so must be terminated by the ISP stage of thymocyte development. ..
- Lin H, Grosschedl R. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature. 1995;376:263-7 pubmed
- Maki K, Sunaga S, Ikuta K. The V-J recombination of T cell receptor-gamma genes is blocked in interleukin-7 receptor-deficient mice. J Exp Med. 1996;184:2423-7 pubmed..These data demonstrated that the V-J recombination of the TCR gamma genes is specifically blocked in the IL-7R-deficient mice and suggested the presence of highly specific regulation for TCR gamma gene rearrangement. ..
- Malek T, Porter B, He Y. Multiple gamma c-dependent cytokines regulate T-cell development. Immunol Today. 1999;20:71-6 pubmed..Here, Thomas Malek and colleagues discuss the contribution of individual gamma c-dependent cytokines in both conventional and intraepithelial T-cell development. ..
- Yoshida H, Honda K, Shinkura R, Adachi S, Nishikawa S, Maki K, et al. IL-7 receptor alpha+ CD3(-) cells in the embryonic intestine induces the organizing center of Peyer's patches. Int Immunol. 1999;11:643-55 pubmed..Intestinal IL-7Ralpha+ cells are lymphoid in morphology but CD3(-) and functional in both nu/nu and Rag2-/- mice. These results implicate IL-7Ralpha+ CD3(-) cells as the direct inducer of the organizing center of PP. ..
- Adachi S, Yoshida H, Honda K, Maki K, Saijo K, Ikuta K, et al. Essential role of IL-7 receptor alpha in the formation of Peyer's patch anlage. Int Immunol. 1998;10:1-6 pubmed..These results indicate that IL-7Ralpha is an essential signal for an early step of PP anlage formation, without which the subsequent processes cannot be initiated. ..
- Goetz C, Harmon I, O Neil J, Burchill M, Farrar M. STAT5 activation underlies IL7 receptor-dependent B cell development. J Immunol. 2004;172:4770-8 pubmedSignals initiated by the IL7R are required for B cell development. However, the roles that distinct IL7R-induced signaling pathways play in this process remains unclear...
- Prockop S, Petrie H. Regulation of thymus size by competition for stromal niches among early T cell progenitors. J Immunol. 2004;173:1604-11 pubmed..Together with asymmetric use of marrow-derived progenitors to reconstitute the intrathymic pool, these processes facilitate continuous generation of new T cells while maintaining a relatively stable organ size. ..
- Vang K, Yang J, Mahmud S, Burchill M, Vegoe A, Farrar M. IL-2, -7, and -15, but not thymic stromal lymphopoeitin, redundantly govern CD4+Foxp3+ regulatory T cell development. J Immunol. 2008;181:3285-90 pubmed
- Kikuchi K, Kasai H, Watanabe A, Lai A, Kondo M. IL-7 specifies B cell fate at the common lymphoid progenitor to pre-proB transition stage by maintaining early B cell factor expression. J Immunol. 2008;181:383-92 pubmed..Therefore, the primary function of IL-7 before the pre-proB stage in B cell development is to maintain the EBF expression level above a certain threshold, which is necessary for pre-proB cells to further transit to the proB stage. ..
- Powell N, Walker A, Stolarczyk E, Canavan J, Gökmen M, Marks E, et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity. 2012;37:674-84 pubmed publisher..Taken together, these data demonstrate the mechanism by which T-bet regulates the complex interplay between mucosal dendritic cells, ILCs, and the intestinal microbiota. ..
- 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
- Crompton T, Outram S, Buckland J, Owen M. A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor alpha chain-deficient mice. Eur J Immunol. 1997;27:100-4 pubmed..In contrast, once cells have progressed beyond the DN stage of development the IL-7R alpha chain becomes no longer essential for RAG expression. ..
- Perumal N, Kenniston T, Tweardy D, Dyer K, Hoffman R, Peschon J, et al. TCR-gamma genes are rearranged but not transcribed in IL-7R alpha-deficient mice. J Immunol. 1997;158:5744-50 pubmed
- 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. ..
- Vondenhoff M, Greuter M, Goverse G, Elewaut D, Dewint P, Ware C, et al. LTbetaR signaling induces cytokine expression and up-regulates lymphangiogenic factors in lymph node anlagen. J Immunol. 2009;182:5439-45 pubmed publisher..Furthermore, the same signals may regulate lymphangiogenesis to the lymph node through induction of VEGF-C. ..
- Burchill M, Yang J, Vogtenhuber C, Blazar B, Farrar M. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol. 2007;178:280-90 pubmed..Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rbeta-dependent STAT5 activation promotes Treg differentiation by regulating expression of foxp3. ..
- 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. ..
- Sitnicka E, Buza Vidas N, Ahlenius H, Cilio C, Gekas C, Nygren J, et al. Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and regulation of lymphoid-primed multipotent progenitors. Blood. 2007;110:2955-64 pubmed
- Maki K, Sunaga S, Komagata Y, Kodaira Y, Mabuchi A, Karasuyama H, et al. Interleukin 7 receptor-deficient mice lack gammadelta T cells. Proc Natl Acad Sci U S A. 1996;93:7172-7 pubmed..On the contrary, it is suggested that NK-cell development requires cytokine(s) other than IL-7. ..
- Honda K, Nakano H, Yoshida H, Nishikawa S, Rennert P, Ikuta K, et al. Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis. J Exp Med. 2001;193:621-30 pubmed..Thus, promotion of PP development relies on mutual interaction between mesenchymal and lymphoid cells. ..
- 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. ..
- 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...
- Schlenner S, Madan V, Busch K, Tietz A, Läufle C, Costa C, et al. Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus. Immunity. 2010;32:426-36 pubmed publisher..We generated interleukin-7 receptor alpha (Il7r) Cre recombinase knockin mice and traced lymphocyte development by visualizing the history of Il7r expression...
- Brickshawana A, Shapiro V, Kita H, Pease L. Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow. J Immunol. 2011;187:5795-804 pubmed publisher..Thus, we identify the enigmatic bone marrow LSK(-)CD25(+) cells as IL-33 responsive, both in vitro and in vivo, with attributes similar to other type 2 innate cells described in peripheral tissues. ..
- Kerdiles Y, Beisner D, Tinoco R, Dejean A, Castrillon D, Depinho R, et al. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat Immunol. 2009;10:176-84 pubmed publisher..severe defect in interleukin 7 receptor alpha-chain (IL-7Ralpha) expression associated with its ability to bind an Il7r enhancer. Finally, growth factor withdrawal induced a Foxo1-dependent increase in Sell, Klf2 and Il7r expression...
- Candeias S, Muegge K, Durum S. IL-7 receptor and VDJ recombination: trophic versus mechanistic actions. Immunity. 1997;6:501-8 pubmed
- Jensen C, Kharazi S, Böiers C, Cheng M, Lübking A, Sitnicka E, et al. FLT3 ligand and not TSLP is the key regulator of IL-7-independent B-1 and B-2 B lymphopoiesis. Blood. 2008;112:2297-304 pubmed publisher..Thus, the same IL-7- and FLT3 ligand-mediated signal-ing regulates alternative pathways of fetal and adult B-1 and B-2 lymphopoiesis. ..
- Min B, Yamane H, Hu Li J, Paul W. Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms. J Immunol. 2005;174:6039-44 pubmed..Our results reveal the complexity and heterogeneity of lymphopenia-driven T cell proliferation and suggest that they may have fundamentally distinct roles in the maintenance of CD4 T cell homeostasis. ..
- Eberl G, Marmon S, Sunshine M, Rennert P, Choi Y, Littman D. An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells. Nat Immunol. 2004;5:64-73 pubmed..This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues. ..
- Schlissel M, Durum S, Muegge K. The interleukin 7 receptor is required for T cell receptor gamma locus accessibility to the V(D)J recombinase. J Exp Med. 2000;191:1045-50 pubmed..We found a reduction in chromatin accessibility for Rag-mediated cleavage in IL-7R-/- thymocytes compared with wild-type. Thus, IL-7 controls recombination at the TCR-gamma locus by regulating locus accessibility. ..
- Durum S, Candeias S, Nakajima H, Leonard W, Baird A, Berg L, et al. Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibility. J Exp Med. 1998;188:2233-41 pubmed..This data supports the model that IL-7R promotes TCR-gamma gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus. ..
- Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature. 2010;463:540-4 pubmed publisher..These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R...
- 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. ..
- Hoyler T, Klose C, Souabni A, Turqueti Neves A, Pfeifer D, Rawlins E, et al. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity. 2012;37:634-48 pubmed publisher..Thus, our data demonstrate that GATA-3 is essential for ILC2 fate decisions and reveal similarities between the transcriptional programs controlling ILC and T helper cell fates. ..
- Simonetta F, Gestermann N, Martinet K, Boniotto M, Tissieres P, Seddon B, et al. Interleukin-7 influences FOXP3+CD4+ regulatory T cells peripheral homeostasis. PLoS ONE. 2012;7:e36596 pubmed publisher..Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance. ..
- Fukuyama S, Hiroi T, Yokota Y, Rennert P, Yanagita M, Kinoshita N, et al. Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gene and CD3(-)CD4(+)CD45(+) cells. Immunity. 2002;17:31-40 pubmed
- Simonetta F, Chiali A, Cordier C, Urrutia A, Girault I, Bloquet S, et al. Increased CD127 expression on activated FOXP3+CD4+ regulatory T cells. Eur J Immunol. 2010;40:2528-38 pubmed publisher..In addition, Treg are also characterized by low CD127 (IL-7R alpha) expression when compared to conventional T cells and their biology in the periphery is considered ..
- 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. ..
- Yu Q, Erman B, Bhandoola A, Sharrow S, Singer A. In vitro evidence that cytokine receptor signals are required for differentiation of double positive thymocytes into functionally mature CD8+ T cells. J Exp Med. 2003;197:475-87 pubmed..Thus, cytokine receptors provide both survival and trophic/differentiative signals with varying degrees of redundancy that are required for differentiation of signaled DP thymocytes into functionally mature CD8(+) T cells. ..
- Luther S, Ansel K, Cyster J. Overlapping roles of CXCL13, interleukin 7 receptor alpha, and CCR7 ligands in lymph node development. J Exp Med. 2003;197:1191-8 pubmed..These findings indicate that CXCL13 and CCR7 ligands promote accumulation of CD4+ CD3- IL-7R alpha hi cells, delivering IL-7R alpha-dependent LT alpha 1 beta 2 signals critical for LN development. ..
- Molofsky A, Nussbaum J, Liang H, Van Dyken S, Cheng L, Mohapatra A, et al. Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med. 2013;210:535-49 pubmed publisher..Thus, ILC2s are resident in VAT and promote eosinophils and AAM implicated in metabolic homeostasis, and this axis is enhanced during Th2-associated immune stimulation. ..
- Vondenhoff M, Desanti G, Cupedo T, Bertrand J, Cumano A, Kraal G, et al. Separation of splenic red and white pulp occurs before birth in a LTalphabeta-independent manner. J Leukoc Biol. 2008;84:152-61 pubmed publisher..The postnatal development of the splenic white pulp, involving the influx of T cells, depends on LTalpha1beta2 expressed by B cells. ..
- 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..Consequently, IL7R expression is reduced on T cells that have received cytokine-mediated survival signals so they do not compete with ..
- Osborne L, Dhanji S, Snow J, Priatel J, Ma M, Miners M, et al. Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7R alpha mutant mice. J Exp Med. 2007;204:619-31 pubmedLoss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Ralpha, CD127) results in severe immunodeficiencies in mice and humans...
- Yao Z, Cui Y, Watford W, Bream J, Yamaoka K, Hissong B, et al. Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci U S A. 2006;103:1000-5 pubmed..Thus, deficiency of Stat5 results in severe combined immunodeficiency, similar in many respects to deficiency of IL-7R, gammac, and Jak3. ..
- 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. ..