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[[X-linked severe combined immunodeficiency]] is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID).<ref name="pmid11037300">{{cite journal | author = Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S, Hammarström L, Hershfield MS, Heyworth PG, Hsu AP, Lähdesmäki A, Lappalainen I, Notarangelo LD, Puck JM, Reith W, Roos D, Schumacher RF, Schwarz K, Vezzoni P, Villa A, Väliaho J, Smith CI | title = Primary immunodeficiency mutation databases | journal = Adv. Genet. | volume = 43 | issue = | pages = 103–88 | year = 2001 | pmid = 11037300 | doi = }}</ref> Most of these mutations involve changes in one or a few DNA building blocks (nucleotides) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein {{Citation needed|date=February 2011}} or no production of protein.<ref name="pmid7883965">{{cite journal | author = Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS | title = Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency | journal = J. Clin. Invest. | volume = 95 | issue = 3 | pages = 1169–73 | year = 1995 | month = March | pmid = 7883965 | pmc = 441454 | doi = 10.1172/JCI117765 }}</ref> Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful [[bone marrow transplant]]ation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, [[T-cell]] and [[NK cell]] populations respectively fail to develop.
[[X-linked severe combined immunodeficiency]] is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID).<ref name="pmid11037300">{{cite journal | author = Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S, Hammarström L, Hershfield MS, Heyworth PG, Hsu AP, Lähdesmäki A, Lappalainen I, Notarangelo LD, Puck JM, Reith W, Roos D, Schumacher RF, Schwarz K, Vezzoni P, Villa A, Väliaho J, Smith CI | title = Primary immunodeficiency mutation databases | journal = Adv. Genet. | volume = 43 | issue = | pages = 103–88 | year = 2001 | pmid = 11037300 | doi = }}</ref> Most of these mutations involve changes in one or a few DNA building blocks (nucleotides) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein {{Citation needed|date=February 2011}} or no production of protein.<ref name="pmid7883965">{{cite journal | author = Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS | title = Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency | journal = J. Clin. Invest. | volume = 95 | issue = 3 | pages = 1169–73 | year = 1995 | month = March | pmid = 7883965 | pmc = 441454 | doi = 10.1172/JCI117765 }}</ref> Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful [[bone marrow transplant]]ation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, [[T-cell]] and [[NK cell]] populations respectively fail to develop.


Experiments in animal models has shown X-SCID to occur similarly in dogs, but not in mice.<ref name="pmid7829104">{{cite journal | author = Henthorn PS, Somberg RL, Fimiani VM, Puck JM, Patterson DF, Felsburg PJ | title = IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease | journal = Genomics | volume = 23 | issue = 1 | pages = 69–74 | year = 1994 | month = September | pmid = 7829104 | doi = 10.1006/geno.1994.1460 | url = | issn = }}</ref>
Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.<ref name="pmid7829104">{{cite journal | author = Henthorn PS, Somberg RL, Fimiani VM, Puck JM, Patterson DF, Felsburg PJ | title = IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease | journal = Genomics | volume = 23 | issue = 1 | pages = 69–74 | year = 1994 | month = September | pmid = 7829104 | doi = 10.1006/geno.1994.1460 | url = | issn = }}</ref>


==References==
==References==

Revision as of 10:12, 15 November 2012

Template:PBB The common gamma chain (γc) (or CD132), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4,[1] IL-7,[2] IL-9, IL-15[3] and interleukin-21 receptor. The γc glycoprotein is a member of the type I cytokine receptor family expressed on most lymphocyte (white blood cell) populations, and its gene is found on the X-chromosome of mammals.

This protein is located on the surface of immature blood-forming cells in bone marrow. One end of the protein resides outside of the cell where it binds to cytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cells, B cells, and natural killer cells. These cells kill viruses, make antibodies, and help regulate the entire immune system.

Gene

Cytokine receptor common subunit gamma also known as interleukin-2 receptor subunit gamma or IL-2RG is a protein that in humans is encoded by the IL2RG gene.[4] The human IL2RG gene is located on the long (q) arm of the X chromosome at position 13.1, from base pair 70,110,279 to base pair 70,114,423.

IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)

Structure

The γc chain is an integral membrane protein that contains extracellular, transmembrane, and intracellular domains.

Function

Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit signals from one cell to another and direct programs of cellular differentiation.

Ligands

The γc chain partners with other ligand-specific receptors to direct lymphocytes to respond to cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.[5]

Signalling

IL2RG has been shown to interact with Janus kinase 3.[6][7]

Clinical significance

X-linked severe combined immunodeficiency

X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID).[8] Most of these mutations involve changes in one or a few DNA building blocks (nucleotides) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein [citation needed] or no production of protein.[9] Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful bone marrow transplantation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.

Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.[10]

References

  1. ^ Russell SM, Keegan AD, Harada N, Nakamura Y, Noguchi M, Leland P, Friedmann MC, Miyajima A, Puri RK, Paul WE (1993). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor". Science. 262 (5141): 1880–3. doi:10.1126/science.8266078. PMID 8266078. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Noguchi M, Nakamura Y, Russell SM, Ziegler SF, Tsang M, Cao X, Leonard WJ (1993). "Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor". Science. 262 (5141): 1877–80. doi:10.1126/science.8266077. PMID 8266077. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Giri JG, Kumaki S, Ahdieh M, Friend DJ, Loomis A, Shanebeck K, DuBose R, Cosman D, Park LS, Anderson DM (1995). "Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor". EMBO J. 14 (15): 3654–63. PMC 394440. PMID 7641685. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Takeshita T, Asao H, Ohtani K, Ishii N, Kumaki S, Tanaka N, Munakata H, Nakamura M, Sugamura K (1992). "Cloning of the gamma chain of the human IL-2 receptor". Science. 257 (5068): 379–82. doi:10.1126/science.1631559. PMID 1631559. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Asao H, Okuyama C, Kumaki S, Ishii N, Tsuchiya S, Foster D, Sugamura K (2001). "Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex". J. Immunol. 167 (1): 1–5. PMID 11418623. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  6. ^ Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN (1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits". Science. 266 (5187): 1045–7. doi:10.1126/science.7973659. PMID 7973659. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O (1994). "Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID". Science. 266 (5187): 1042–5. doi:10.1126/science.7973658. PMID 7973658. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S, Hammarström L, Hershfield MS, Heyworth PG, Hsu AP, Lähdesmäki A, Lappalainen I, Notarangelo LD, Puck JM, Reith W, Roos D, Schumacher RF, Schwarz K, Vezzoni P, Villa A, Väliaho J, Smith CI (2001). "Primary immunodeficiency mutation databases". Adv. Genet. 43: 103–88. PMID 11037300.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Schmalstieg FC, Leonard WJ, Noguchi M, Berg M, Rudloff HE, Denney RM, Dave SK, Brooks EG, Goldman AS (1995). "Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency". J. Clin. Invest. 95 (3): 1169–73. doi:10.1172/JCI117765. PMC 441454. PMID 7883965. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Henthorn PS, Somberg RL, Fimiani VM, Puck JM, Patterson DF, Felsburg PJ (1994). "IL-2R gamma gene microdeletion demonstrates that canine X-linked severe combined immunodeficiency is a homologue of the human disease". Genomics. 23 (1): 69–74. doi:10.1006/geno.1994.1460. PMID 7829104. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Further reading

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