IL7R Gene

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1		Dean Liu	+ 714 word(s)	714	2020-12-15 07:57:26

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/il7r

Interleukin 7 receptor

genes

1. Introduction

The IL7R gene provides instructions for making a protein called interleukin 7 (IL-7) receptor alpha chain. This protein is one piece of both the IL-7 receptor and the thymic stromal lymphopoietin (TSLP) receptor. These receptors are embedded in the cell membrane of immune system cells. The IL-7 receptor is found in B cells and T cells as well as the early blood-forming cells that give rise to them. The TSLP receptor is found in several types of immune cells, including B cells, T cells, monocytes, and dendritic cells. These cells identify foreign substances and defend the body against infection and disease.

At the cell surface, the IL-7 receptor interacts with a protein called IL-7. IL-7 is a cytokine, which is a protein that regulates the activity of immune system cells. The receptor and cytokine fit together like a lock and its key, triggering a series of chemical signals inside the cell. In early blood-forming cells, signaling through the IL-7 receptor ensures the development of mature B cells and T cells. IL-7 receptor signaling also stimulates the later growth and division (proliferation) and survival of these cells.

Similarly, the TSLP receptor interacts with the cytokine TSLP. Attachment of TSLP to its receptor triggers a set of signals that support proliferation and maturation of a variety of immune system cells.

2. Health Conditions Related to Genetic Changes

2.1. Multiple Sclerosis

A common variation of the IL-7R gene increases the risk of developing multiple sclerosis. This condition affects the brain and spinal cord (central nervous system), causing muscle weakness, poor coordination, numbness, and a variety of other health problems. The genetic variation involved in multiple sclerosis affects a single protein building block (amino acid) in the IL-7 receptor alpha chain, specifying the amino acid isoleucine at position 244 instead of the amino acid threonine (written as Thr244Ile). The IL-7 receptor that contains this version of the alpha chain is not embedded in the cell surface but is instead found inside the cell. It is not clear if this alpha chain variant affects the TSLP receptor.

Because the IL7R gene is involved in regulation of the immune system, changes in it might be involved in the autoimmune response and inflammation that damage nerves and the protective coating surrounding them (the myelin sheath), leading to the signs and symptoms of multiple sclerosis. (Autoimmunity occurs when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.) However, it is unclear exactly what role the IL-7R gene variant plays in development of multiple sclerosis. It is likely that a combination of genetic and environmental factors is involved.

2.2. Other Disorders

Mutations in the IL7R gene can cause a form of severe combined immunodeficiency (SCID), in which affected individuals have decreased immune function and are prone to recurrent and persistent infections. Affected individuals with IL7R gene mutations have few or no T cells but normal numbers of B cells and another type of immune cell called NK cells. This form of the condition is called T^-B⁺NK⁺ SCID. Many IL7R gene mutations that cause SCID prevent the production of the IL-7 receptor alpha chain, which impairs IL-7 receptor and TSLP receptor signaling. Without this signaling, development of T cells is disrupted. A lack of T cells reduces the immune system's ability to fight infections, leading to recurrent infections in people with T^-B⁺NK⁺ SCID.

Mutations in the IL7R gene can also cause cancers of blood-forming cells, specifically B-cell acute lymphoblastic leukemia (ALL), which is characterized by elevated numbers of B cells in the blood, and T-cell ALL, characterized by elevated numbers of T cells. The mutations associated with these cancers lead to an altered IL-7 receptor alpha chain. With this alteration, signaling pathways like those triggered by the IL-7 receptor or the TSLP receptor are constantly turned on (constitutively active) even without cytokine interaction. Constant signaling increases proliferation and survival of B cells or T cells, leading to ALL.

3. Other Names for This Gene

CD127
CD127 antigen
CDW127
IL-7 receptor subunit alpha
IL-7R subunit alpha
IL-7R-alpha
IL-7RA
IL7RA
IL7RA_HUMAN
ILRA
interleukin 7 receptor alpha chain
interleukin 7 receptor isoform H5-6
interleukin-7 receptor subunit alpha
interleukin-7 receptor subunit alpha precursor

References

Akashi K, Kondo M, Weissman IL. Role of interleukin-7 in T-cell developmentfrom hematopoietic stem cells. Immunol Rev. 1998 Oct;165:13-28. Review.
Corfe SA, Paige CJ. The many roles of IL-7 in B cell development; mediator of survival, proliferation and differentiation. Semin Immunol. 2012Jun;24(3):198-208. doi: 10.1016/j.smim.2012.02.001.
Giliani S, Mori L, de Saint Basile G, Le Deist F, Rodriguez-Perez C, Forino C,Mazzolari E, Dupuis S, Elhasid R, Kessel A, Galambrun C, Gil J, Fischer A,Etzioni A, Notarangelo LD. Interleukin-7 receptor alpha (IL-7Ralpha) deficiency: cellular and molecular bases. Analysis of clinical, immunological, and molecular features in 16 novel patients. Immunol Rev. 2005 Feb;203:110-26. Review.
Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, Caillier SJ,Ban M, Goris A, Barcellos LF, Lincoln R, McCauley JL, Sawcer SJ, Compston DA,Dubois B, Hauser SL, Garcia-Blanco MA, Pericak-Vance MA, Haines JL; MultipleSclerosis Genetics Group. Interleukin 7 receptor alpha chain (IL7R) shows allelicand functional association with multiple sclerosis. Nat Genet. 2007Sep;39(9):1083-91.
He R, Geha RS. Thymic stromal lymphopoietin. Ann N Y Acad Sci. 2010Jan;1183:13-24. doi: 10.1111/j.1749-6632.2009.05128.x. Review.
Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallström E, Khademi M, Oturai A, Ryder LP, Saarela J, Harbo HF, Celius EG, Salter H, Olsson T, Hillert J.Variation in interleukin 7 receptor alpha chain (IL7R) influences risk ofmultiple sclerosis. Nat Genet. 2007 Sep;39(9):1108-13.
Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression inT(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet. 1998 Dec;20(4):394-7.
Shochat C, Tal N, Bandapalli OR, Palmi C, Ganmore I, te Kronnie G, Cario G,Cazzaniga G, Kulozik AE, Stanulla M, Schrappe M, Biondi A, Basso G, Bercovich D, Muckenthaler MU, Izraeli S. Gain-of-function mutations in interleukin-7receptor-α (IL7R) in childhood acute lymphoblastic leukemias. J Exp Med. 2011 May9;208(5):901-8. doi: 10.1084/jem.20110580.Med. 2011 Jun 6;208(6):1333. J Exp Med. 2011 May 9;208(5):preceding 901.
Zenatti PP, Ribeiro D, Li W, Zuurbier L, Silva MC, Paganin M, Tritapoe J,Hixon JA, Silveira AB, Cardoso BA, Sarmento LM, Correia N, Toribio ML, Kobarg J, Horstmann M, Pieters R, Brandalise SR, Ferrando AA, Meijerink JP, Durum SK, YunesJA, Barata JT. Oncogenic IL7R gain-of-function mutations in childhood T-cellacute lymphoblastic leukemia. Nat Genet. 2011 Sep 4;43(10):932-9. doi:10.1038/ng.924.

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Subjects: Genetics & Heredity

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Dean Liu

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Entry Collection: MedlinePlus

Update Date: 23 Dec 2020

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