Interleukin 7: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Interleukin 7''' ('''IL-7''') is a [[protein]]<ref name="pmid3259677">{{cite journal |vauthors=Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S | title = Stimulation of B-cell progenitors by cloned murine interleukin-7 | journal = Nature | volume = 333 | issue = 6173 | pages = 571–3 |date=June 1988 | pmid = 3259677 | doi = 10.1038/333571a0 | url =  |bibcode = 1988Natur.333..571N }}</ref> that in humans is encoded by the ''IL7'' [[gene]].<ref name="pmid2643102">{{cite journal |vauthors=Goodwin RG, Lupton S, Schmierer A, Hjerrild KJ, Jerzy R, Clevenger W, Gillis S, Cosman D, Namen AE | title = Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 1 | pages = 302–6 |date=January 1989 | pmid = 2643102 | pmc = 286452 | doi = 10.1073/pnas.86.1.302| url =  |bibcode = 1989PNAS...86..302G }}</ref><ref name="pmid2786840">{{cite journal |vauthors=Sutherland GR, Baker E, Fernandez KE, Callen DF, Goodwin RG, Lupton S, Namen AE, Shannon MF, Vadas MA | title = The gene for human interleukin 7 (IL7) is at 8q12-13 | journal = Hum. Genet. | volume = 82 | issue = 4 | pages = 371–2 |date=July 1989 | pmid = 2786840 | doi = 10.1007/BF00274000| url =  }}</ref><ref>{{cite journal  |vauthors=Lupton SD, Gimpel S, Jerzy R, etal |title=Characterization of the human and murine IL-7 genes |journal=J. Immunol. |volume=144 |issue= 9 |pages= 3592–601 |year= 1990 |pmid= 2329282 |doi= }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
IL-7 is a [[Haematopoiesis|hematopoietic]] [[growth factor]] secreted by [[stromal cell]]s in the [[bone marrow]] and [[thymus]]. It is also produced by [[keratinocyte]]s,<ref>{{cite journal |vauthors=Heufler C, Topar G, Grasseger A, etal |title=Interleukin 7 is produced by murine and human keratinocytes |journal=J. Exp. Med. |volume=178 |issue=3 |pages=1109–14 |date=September 1993 |pmid=8350050 |pmc=2191157 |doi= 10.1084/jem.178.3.1109|url=}}</ref> [[dendritic cell]]s,<ref>{{cite journal |vauthors=Kröncke R, Loppnow H, Flad HD, Gerdes J |title=Human follicular dendritic cells and vascular cells produce interleukin-7: a potential role for interleukin-7 in the germinal center reaction |journal=Eur. J. Immunol. |volume=26 |issue=10 |pages=2541–4 |date=October 1996 |pmid=8898972 |doi=10.1002/eji.1830261040 |url=}}</ref> [[hepatocyte]]s,<ref>{{cite journal  |vauthors=Sawa Y, Arima Y, Ogura H, etal |title=Hepatic interleukin-7 expression regulates T cell responses |journal=Immunity |volume=30 |issue=3 |pages=447–57 |date=March 2009 |pmid=19285437 |doi=10.1016/j.immuni.2009.01.007 |url=}}</ref> [[neuron]]s, and [[epithelial cells]],<ref>{{cite journal  |vauthors=Watanabe M, Ueno Y, Yajima T, etal |title=Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes |journal=J. Clin. Invest. |volume=95 |issue= 6 |pages= 2945–53 |year= 1995 |pmid= 7769137 |doi=10.1172/JCI118002  | pmc=295983  }}</ref> but is not produced by normal [[lymphocyte]]s.<ref name="Fry TJ, Mackall CL 2002 3892–904">{{cite journal |vauthors=Fry TJ, Mackall CL | title = Interleukin-7: from bench to clinic | journal = Blood | volume = 99 | issue = 11 | pages = 3892–904 |date=June 2002 | pmid = 12010786 | doi = 10.1182/blood.V99.11.3892 | url = }}</ref>
{{GNF_Protein_box
  | image =
| image_source = 
| PDB =
| Name = Interleukin 7
| HGNCid = 6023
| Symbol = IL7
| AltSymbols =; IL-7
| OMIM = 146660
| ECnumber =
| Homologene = 680
| MGIid = 96561
| GeneAtlas_image1 = PBB_GE_IL7_206693_at_tn.png
| Function = {{GNF_GO|id=GO:0005139 |text = interleukin-7 receptor binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}}
| Process = {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0006959 |text = humoral immune response}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}} {{GNF_GO|id=GO:0009887 |text = organ morphogenesis}} {{GNF_GO|id=GO:0030890 |text = positive regulation of B cell proliferation}} {{GNF_GO|id=GO:0043066 |text = negative regulation of apoptosis}} {{GNF_GO|id=GO:0045453 |text = bone resorption}} {{GNF_GO|id=GO:0045582 |text = positive regulation of T cell differentiation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3574
    | Hs_Ensembl = ENSG00000104432
    | Hs_RefseqProtein = NP_000871
    | Hs_RefseqmRNA = NM_000880
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 8
    | Hs_GenLoc_start = 79807564
    | Hs_GenLoc_end = 79880313
    | Hs_Uniprot = P13232
    | Mm_EntrezGene = 16196
    | Mm_Ensembl = ENSMUSG00000040329
    | Mm_RefseqmRNA = NM_008371
    | Mm_RefseqProtein = NP_032397
    | Mm_GenLoc_db =
    | Mm_GenLoc_chr = 3
    | Mm_GenLoc_start = 7556913
    | Mm_GenLoc_end = 7587247
    | Mm_Uniprot = Q3UT18
  }}
}}
'''Interleukin 7''' ('''IL7''') is a hematopoietic [[growth factor]] secreted by the stromal cells of the red marrow and thymus capable of stimulating the proliferation of [[lymphoid]] progenitors. It is important for proliferation during certain stages of [[B-cell]] maturation, [[T Lymphocyte|T]] and [[NK cell]] survival, development and homeostasis (From [[UniProt]] IL7_HUMAN).


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{PBB_Summary
| section_title =  
| summary_text = The protein encoded by this gene is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRB) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.<ref>{{cite web | title = Entrez Gene: IL7 interleukin 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3574| accessdate = }}</ref>
}}


The three-dimensional structure of IL-7 in complex with the [[ectodomain]] of [[IL7R]] has been determined using [[X-ray crystallography#Biological macromolecular crystallography|X-ray diffraction]].<ref name="pmid19141282">{{cite journal |vauthors=McElroy CA, Dohm JA, Walsh ST | title = Structural and biophysical studies of the human IL-7/IL-7Ralpha complex | journal = Structure | volume = 17 | issue = 1 | pages = 54–65 |date=January 2009 | pmid = 19141282 | pmc = 2654238 | doi = 10.1016/j.str.2008.10.019 }}</ref>


==References==
== Function ==
{{reflist|2}}
 
==Further reading==
=== Lymphocyte maturation ===
* [http://bloodjournal.hematologylibrary.org/cgi/content/full/99/11/3892  Terry J. Fry and Crystal L. Mackall, "Interleukin-7: from bench to clinic", ''Blood,'' Vol. 99, No. 11, pp. 3892-3904. Review article (1 June 2002)]
 
{{refbegin | 2}}
IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic [[stem cell]]s into [[lymphoid progenitor cell]]s (as opposed to myeloid progenitor cells where differentiation is stimulated by [[Interleukin 3|IL-3]]).{{citation needed|date=February 2011}} It also stimulates proliferation of all cells in the lymphoid lineage ([[B cell]]s, [[T cell]]s and [[natural killer cell|NK cells]]).{{citation needed|date=February 2011}} It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and [[homeostasis]].{{citation needed|date=February 2011}}
{{PBB_Further_reading
 
| citations =  
IL-7 is a [[cytokine]] important for B and T cell development. This cytokine and the hepatocyte growth factor ([[Hepatocyte growth factor|HGF]]) form a [[heterodimer]] that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development.<ref>{{cite journal |vauthors=Muegge K, Vila MP, Durum SK |title=Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene |journal=Science |volume=261 |issue=5117 |pages=93–5 |date=July 1993 |pmid=7686307 |doi= 10.1126/science.7686307|url= |bibcode=1993Sci...261...93M}}</ref> This cytokine can be produced locally by intestinal epithelial and epithelial [[goblet cell]]s, and may serve as a regulatory factor for intestinal mucosal lymphocytes.{{citation needed|date=February 2011}} [[Knockout studies]] in mice suggested that this cytokine plays an essential role in lymphoid cell survival.<ref>{{cite web | title = Entrez Gene: IL7 interleukin 7| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3574| accessdate = }}</ref>
*{{cite journal | author=Möller P, Böhm M, Czarnetszki BM, Schadendorf D |title=Interleukin-7. Biology and implications for dermatology. |journal=Exp. Dermatol. |volume=5 |issue= 3 |pages= 129-37 |year= 1997 |pmid= 8840152 |doi= }}
 
*{{cite journal  | author=Appasamy PM |title=Biological and clinical implications of interleukin-7 and lymphopoiesis. |journal=Cytokines Cell. Mol. Ther. |volume=5 |issue= 1 |pages= 25-39 |year= 1999 |pmid= 10390077 |doi=  }}
=== IL-7 signaling ===
*{{cite journal  | author=Fry TJ, Mackall CL |title=Interleukin-7: from bench to clinic. |journal=Blood |volume=99 |issue= 11 |pages= 3892-904 |year= 2002 |pmid= 12010786 |doi=  }}
 
*{{cite journal  | author=Fry TJ, Mackall CL |title=Interleukin-7 and immunorestoration in HIV: beyond the thymus. |journal=J. Hematother. Stem Cell Res. |volume=11 |issue= 5 |pages= 803-7 |year= 2003 |pmid= 12427286 |doi= 10.1089/152581602760404603 }}
[[File:IL-7receptor and signaling.jpg|thumb|300px|left|'''IL-7 receptor and signaling''', common γ chain (blue) and IL-7 receptor-α (green)]]
*{{cite journal  | author=Al-Rawi MA, Mansel RE, Jiang WG |title=Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours. |journal=Histol. Histopathol. |volume=18 |issue= 3 |pages= 911-23 |year= 2004 |pmid= 12792903 |doi=  }}
 
*{{cite journal | author=Aspinall R, Henson S, Pido-Lopez J, Ngom PT |title=Interleukin-7: an interleukin for rejuvenating the immune system. |journal=Ann. N. Y. Acad. Sci. |volume=1019 |issue= |pages= 116-22 |year= 2004 |pmid= 15247003 |doi= 10.1196/annals.1297.021 }}
IL-7 binds to the [[Interleukin-7 receptor|IL-7 receptor]], a heterodimer consisting of [[CD127|Interleukin-7 receptor alpha]] and [[CD132|common gamma chain receptor]].<ref>{{cite journal   |vauthors=Noguchi M, Nakamura Y, Russell SM, etal |title=Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor |journal=Science |volume=262 |issue= 5141 |pages= 1877–80 |year= 1994 |pmid= 8266077 |doi=10.1126/science.8266077  |bibcode = 1993Sci...262.1877N }}</ref> Binding results in a cascade of signals important for T-cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL-7 receptor exhibit thymic [[atrophy]], arrest of T-cell development at the double positive stage, and severe [[lymphopenia]]. Administration of IL-7 to mice results in an increase in recent thymic emigrants, increases in B and T cells, and increased recovery of T cells after [[cyclophosphamide]] administration or after bone marrow transplantation.
*{{cite journal  | author=Snyder KM, Mackall CL, Fry TJ |title=IL-7 in allogeneic transplant: clinical promise and potential pitfalls. |journal=Leuk. Lymphoma |volume=47 |issue= 7 |pages= 1222-8 |year= 2007 |pmid= 16923550 |doi= 10.1080/10428190600555876 }}
 
*{{cite journal  | author=Brunton LL, Lupton SD |title=An STS in the human IL7 gene located at 8q12-13. |journal=Nucleic Acids Res. |volume=18 |issue= 5 |pages= 1315 |year= 1990 |pmid= 2320434 |doi= }}
== Disease ==
*{{cite journal  | author=Lupton SD, Gimpel S, Jerzy R, ''et al.'' |title=Characterization of the human and murine IL-7 genes. |journal=J. Immunol. |volume=144 |issue= 9 |pages= 3592-601 |year= 1990 |pmid= 2329282 |doi=  }}
 
*{{cite journal | author=Goodwin RG, Lupton S, Schmierer A, ''et al.'' |title=Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 1 |pages= 302-6 |year= 1989 |pmid= 2643102 |doi=  }}
=== Cancer ===
*{{cite journal  | author=Sutherland GR, Baker E, Fernandez KE, ''et al.'' |title=The gene for human interleukin 7 (IL7) is at 8q12-13. |journal=Hum. Genet. |volume=82 |issue= 4 |pages= 371-2 |year= 1989 |pmid= 2786840 |doi=  }}
IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma).<ref name="pmid10068062">{{cite journal |vauthors=Or R, Abdul-Hai A, Ben-Yehuda A | title = Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis and immune recovery | journal = Cytokines Cell. Mol. Ther. | volume = 4 | issue = 4 | pages = 287–94 |date=December 1998 | pmid = 10068062 | doi = | url =  }}</ref>
*{{cite journal  | author=Muegge K, Vila MP, Durum SK |title=Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene. |journal=Science |volume=261 |issue= 5117 |pages= 93-5 |year= 1993 |pmid= 7686307 |doi= }}
 
*{{cite journal  | author=Watanabe M, Ueno Y, Yajima T, ''et al.'' |title=Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. |journal=J. Clin. Invest. |volume=95 |issue= 6 |pages= 2945-53 |year= 1995 |pmid= 7769137 |doi= }}
=== Viral Infections ===
*{{cite journal  | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
Elevated levels of IL-7 have also been detected in the plasma of [[HIV|HIV-infected patients]].<ref>{{cite journal  |vauthors=Napolitano LA, Grant RM, Deeks SG, etal |title=Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis |journal=Nat. Med. |volume=7 |issue=1 |pages=73–9 |date=January 2001 |pmid=11135619 |doi=10.1038/83381 |url=}}</ref>
*{{cite journal | author=Noguchi M, Nakamura Y, Russell SM, ''et al.'' |title=Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. |journal=Science |volume=262 |issue= 5141 |pages= 1877-80 |year= 1994 |pmid= 8266077 |doi= }}
 
*{{cite journal  | author=Sica D, Rayman P, Stanley J, ''et al.'' |title=Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell carcinoma. |journal=Int. J. Cancer |volume=53 |issue= 6 |pages= 941-7 |year= 1993 |pmid= 8473051 |doi=  }}
== Clinical application ==
*{{cite journal | author=Kroemer RT, Doughty SW, Robinson AJ, Richards WG |title=Prediction of the three-dimensional structure of human interleukin-7 by homology modeling. |journal=Protein Eng. |volume=9 |issue= 6 |pages= 493-8 |year= 1996 |pmid= 8862549 |doi=  }}
 
*{{cite journal  | author=Kroemer RT, Richards WG |title=Homology modeling study of the human interleukin-7 receptor complex. |journal=Protein Eng. |volume=9 |issue= 12 |pages= 1135-42 |year= 1997 |pmid= 9010926 |doi=  }}
IL-7  as an [[immunotherapy]] agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during [[HIV|HIV infection]].<ref name="Fry TJ, Mackall CL 2002 3892–904"/><ref>{{cite journal  |vauthors=Fry TJ, Mackall CL |title=Interleukin-7 and immunorestoration in HIV: beyond the thymus |journal=J. Hematother. Stem Cell Res. |volume=11 |issue= 5 |pages= 803–7 |year= 2003 |pmid= 12427286 |doi= 10.1089/152581602760404603 }}</ref>
*{{cite journal  | author=Kim JH, Loveland JE, Sitz KV, ''et al.'' |title=Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1. |journal=Clin. Exp. Immunol. |volume=108 |issue= 2 |pages= 243-50 |year= 1997 |pmid= 9158092 |doi= }}
 
}}
=== Cancer ===
{{refend}}
 
[[Recombinant DNA|Recombinant]] IL-7 has been safely administered to patients in several phase I and II [[clinical trials]]. A human study of IL-7 in patients with [[cancer]] demonstrated that administration of this cytokine can transiently disrupt the homeostasis of both CD8+ and CD4+ T cells with a commensurate decrease in the percentage of CD4+CD25+Foxp3+ T regulatory cells.<ref name="pmid16699374">{{cite journal |vauthors=Rosenberg SA, Sportès C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, Stetler-Stevenson M, Morton KE, Mavroukakis SA, Morre M, Buffet R, Mackall CL, Gress RE | title = IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells | journal = J. Immunother. | volume = 29 | issue = 3 | pages = 313–9 | year = 2006 | pmid = 16699374 | pmc = 1473976 | doi = 10.1097/01.cji.0000210386.55951.c2 | url =  }}</ref> No objective cancer regression was observed, however a [[dose limiting toxicity]] (DLT) was not reached in this study due to the development of neutralizing [[antibodies]] against the [[recombinant cytokine]].
 
=== HIV infection ===
 
Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients.<ref name="IL7HIV">{{cite journal  |vauthors=Sereti I, Estes JD, Thompson WL, Morcock DR, Fischl MA, etal | title = Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration | journal = PLoS Pathogens | volume = 10 | issue = 1 | pages = e1003890 | year = 2014| doi = 10.1371/journal.ppat.1003890 | pmid = 24497828 | pmc = 3907377 | url = http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003890 }}</ref>


=== Transplantation ===
IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant.<ref>{{cite journal |vauthors=Snyder KM, Mackall CL, Fry TJ |title=IL-7 in allogeneic transplant: clinical promise and potential pitfalls |journal=Leuk. Lymphoma |volume=47 |issue=7 |pages=1222–8 |date=July 2006 |pmid=16923550 |doi=10.1080/10428190600555876 |url=}}</ref>


{{immunology-stub}}
== References ==
{{Reflist|35em}}


== Further reading ==
{{Refbegin|35em}}
*{{cite journal  |vauthors=Möller P, Böhm M, Czarnetszki BM, Schadendorf D |title=Interleukin-7. Biology and implications for dermatology |journal=Exp. Dermatol. |volume=5 |issue= 3 |pages= 129–37 |year= 1997 |pmid= 8840152 |doi=10.1111/j.1600-0625.1996.tb00107.x  }}
*{{cite journal  | author=Appasamy PM |title=Biological and clinical implications of interleukin-7 and lymphopoiesis |journal=Cytokines Cell. Mol. Ther. |volume=5 |issue= 1 |pages= 25–39 |year= 1999 |pmid= 10390077 |doi=  }}
*{{cite journal  |vauthors=Al-Rawi MA, Mansel RE, Jiang WG |title=Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours |journal=Histol. Histopathol. |volume=18 |issue= 3 |pages= 911–23 |year= 2004 |pmid= 12792903 |doi=  }}
*{{cite journal  |vauthors=Aspinall R, Henson S, Pido-Lopez J, Ngom PT |title=Interleukin-7: an interleukin for rejuvenating the immune system |journal=Ann. N. Y. Acad. Sci. |volume=1019 |issue=  |pages= 116–22 |year= 2004 |pmid= 15247003 |doi= 10.1196/annals.1297.021 |bibcode=2004NYASA1019..116A }}
*{{cite journal  |vauthors=Sica D, Rayman P, Stanley J, etal |title=Interleukin 7 enhances the proliferation and effector function of tumor-infiltrating lymphocytes from renal-cell carcinoma |journal=Int. J. Cancer |volume=53 |issue= 6 |pages= 941–7 |year= 1993 |pmid= 8473051 |doi=10.1002/ijc.2910530613  }}
*{{cite journal  |vauthors=Kim JH, Loveland JE, Sitz KV, etal |title=Expansion of restricted cellular immune responses to HIV-1 envelope by vaccination: IL-7 and IL-12 differentially augment cellular proliferative responses to HIV-1 |journal=Clin. Exp. Immunol. |volume=108 |issue= 2 |pages= 243–50 |year= 1997 |pmid= 9158092 |doi=10.1046/j.1365-2249.1997.d01-1006.x  | pmc=1904649  }}
{{refend}}


{{interleukins}}
{{Interleukins}}
{{Interleukin receptor modulators}}
{{NLM content}}


[[pl:Interleukina 7]]
[[Category:Interleukins]]
{{WikiDoc Sources}}
[[Category:Immunomodulating drugs]]
[[Category:Cancer treatments]]

Latest revision as of 01:29, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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View/Edit Human

Interleukin 7 (IL-7) is a protein[1] that in humans is encoded by the IL7 gene.[2][3][4]

IL-7 is a hematopoietic growth factor secreted by stromal cells in the bone marrow and thymus. It is also produced by keratinocytes,[5] dendritic cells,[6] hepatocytes,[7] neurons, and epithelial cells,[8] but is not produced by normal lymphocytes.[9]

Structure

The three-dimensional structure of IL-7 in complex with the ectodomain of IL7R has been determined using X-ray diffraction.[10]

Function

Lymphocyte maturation

IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3).[citation needed] It also stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and NK cells).[citation needed] It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis.[citation needed]

IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development.[11] This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes.[citation needed] Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.[12]

IL-7 signaling

File:IL-7receptor and signaling.jpg
IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)

IL-7 binds to the IL-7 receptor, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor.[13] Binding results in a cascade of signals important for T-cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL-7 receptor exhibit thymic atrophy, arrest of T-cell development at the double positive stage, and severe lymphopenia. Administration of IL-7 to mice results in an increase in recent thymic emigrants, increases in B and T cells, and increased recovery of T cells after cyclophosphamide administration or after bone marrow transplantation.

Disease

Cancer

IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma).[14]

Viral Infections

Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patients.[15]

Clinical application

IL-7 as an immunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection.[9][16]

Cancer

Recombinant IL-7 has been safely administered to patients in several phase I and II clinical trials. A human study of IL-7 in patients with cancer demonstrated that administration of this cytokine can transiently disrupt the homeostasis of both CD8+ and CD4+ T cells with a commensurate decrease in the percentage of CD4+CD25+Foxp3+ T regulatory cells.[17] No objective cancer regression was observed, however a dose limiting toxicity (DLT) was not reached in this study due to the development of neutralizing antibodies against the recombinant cytokine.

HIV infection

Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients.[18]

Transplantation

IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant.[19]

References

  1. ↑ Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer A, Mosley B, March CJ, Urdal D, Gillis S (June 1988). "Stimulation of B-cell progenitors by cloned murine interleukin-7". Nature. 333 (6173): 571–3. Bibcode:1988Natur.333..571N. doi:10.1038/333571a0. PMID 3259677.
  2. ↑ Goodwin RG, Lupton S, Schmierer A, Hjerrild KJ, Jerzy R, Clevenger W, Gillis S, Cosman D, Namen AE (January 1989). "Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells". Proc. Natl. Acad. Sci. U.S.A. 86 (1): 302–6. Bibcode:1989PNAS...86..302G. doi:10.1073/pnas.86.1.302. PMC 286452. PMID 2643102.
  3. ↑ Sutherland GR, Baker E, Fernandez KE, Callen DF, Goodwin RG, Lupton S, Namen AE, Shannon MF, Vadas MA (July 1989). "The gene for human interleukin 7 (IL7) is at 8q12-13". Hum. Genet. 82 (4): 371–2. doi:10.1007/BF00274000. PMID 2786840.
  4. ↑ Lupton SD, Gimpel S, Jerzy R, et al. (1990). "Characterization of the human and murine IL-7 genes". J. Immunol. 144 (9): 3592–601. PMID 2329282.
  5. ↑ Heufler C, Topar G, Grasseger A, et al. (September 1993). "Interleukin 7 is produced by murine and human keratinocytes". J. Exp. Med. 178 (3): 1109–14. doi:10.1084/jem.178.3.1109. PMC 2191157. PMID 8350050.
  6. ↑ Kröncke R, Loppnow H, Flad HD, Gerdes J (October 1996). "Human follicular dendritic cells and vascular cells produce interleukin-7: a potential role for interleukin-7 in the germinal center reaction". Eur. J. Immunol. 26 (10): 2541–4. doi:10.1002/eji.1830261040. PMID 8898972.
  7. ↑ Sawa Y, Arima Y, Ogura H, et al. (March 2009). "Hepatic interleukin-7 expression regulates T cell responses". Immunity. 30 (3): 447–57. doi:10.1016/j.immuni.2009.01.007. PMID 19285437.
  8. ↑ Watanabe M, Ueno Y, Yajima T, et al. (1995). "Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes". J. Clin. Invest. 95 (6): 2945–53. doi:10.1172/JCI118002. PMC 295983. PMID 7769137.
  9. ↑ 9.0 9.1 Fry TJ, Mackall CL (June 2002). "Interleukin-7: from bench to clinic". Blood. 99 (11): 3892–904. doi:10.1182/blood.V99.11.3892. PMID 12010786.
  10. ↑ McElroy CA, Dohm JA, Walsh ST (January 2009). "Structural and biophysical studies of the human IL-7/IL-7Ralpha complex". Structure. 17 (1): 54–65. doi:10.1016/j.str.2008.10.019. PMC 2654238. PMID 19141282.
  11. ↑ Muegge K, Vila MP, Durum SK (July 1993). "Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene". Science. 261 (5117): 93–5. Bibcode:1993Sci...261...93M. doi:10.1126/science.7686307. PMID 7686307.
  12. ↑ "Entrez Gene: IL7 interleukin 7".
  13. ↑ Noguchi M, Nakamura Y, Russell SM, et al. (1994). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor". Science. 262 (5141): 1877–80. Bibcode:1993Sci...262.1877N. doi:10.1126/science.8266077. PMID 8266077.
  14. ↑ Or R, Abdul-Hai A, Ben-Yehuda A (December 1998). "Reviewing the potential utility of interleukin-7 as a promoter of thymopoiesis and immune recovery". Cytokines Cell. Mol. Ther. 4 (4): 287–94. PMID 10068062.
  15. ↑ Napolitano LA, Grant RM, Deeks SG, et al. (January 2001). "Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis". Nat. Med. 7 (1): 73–9. doi:10.1038/83381. PMID 11135619.
  16. ↑ Fry TJ, Mackall CL (2003). "Interleukin-7 and immunorestoration in HIV: beyond the thymus". J. Hematother. Stem Cell Res. 11 (5): 803–7. doi:10.1089/152581602760404603. PMID 12427286.
  17. ↑ Rosenberg SA, Sportès C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, Stetler-Stevenson M, Morton KE, Mavroukakis SA, Morre M, Buffet R, Mackall CL, Gress RE (2006). "IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells". J. Immunother. 29 (3): 313–9. doi:10.1097/01.cji.0000210386.55951.c2. PMC 1473976. PMID 16699374.
  18. ↑ Sereti I, Estes JD, Thompson WL, Morcock DR, Fischl MA, et al. (2014). "Decreases in Colonic and Systemic Inflammation in Chronic HIV Infection after IL-7 Administration". PLoS Pathogens. 10 (1): e1003890. doi:10.1371/journal.ppat.1003890. PMC 3907377. PMID 24497828.
  19. ↑ Snyder KM, Mackall CL, Fry TJ (July 2006). "IL-7 in allogeneic transplant: clinical promise and potential pitfalls". Leuk. Lymphoma. 47 (7): 1222–8. doi:10.1080/10428190600555876. PMID 16923550.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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