IL2RA

Source: Wikipedia, the free encyclopedia.
"CD25" redirects here. Not to be confused with Cdc25.
IL2RA
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000134460

ENSMUSG00000026770

UniProt

P01589

P01590

RefSeq (mRNA)

NM_000417
NM_001308242
NM_001308243

NM_008367

RefSeq (protein)

NP_000408
NP_001295171
NP_001295172

NP_032393

Location (UCSC)Chr 10: 6.01 – 6.06 MbChr 2: 11.65 – 11.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The Interleukin-2 receptor alpha chain (also called TAC antigen, P55, and mainly CD25) is a protein involved in the assembly of the high-affinity Interleukin-2 receptor, consisting of alpha (IL2RA), beta (

IL2RG). As the name indicates, this receptor interacts with Interleukin-2, a pleiotropic cytokine which plays an important role in immune homeostasis.[5][6]

Genetics

The human protein Interleukin-2 receptor subunit alpha is encoded by a gene called IL2RA with a length around 51,6 kb. Alternative names for this protein coding gene are IL2R, IDDM10 and TCGFR. Location of IL2RA in human genome is on the short arm of 10th chromosome (10p15.1).[7][8][9]

Several frequent point mutations, single nucleotide polymorphism (SNP), have been identified in or in close proximity to IL2RA gene in the population. These SNPs have been linked mainly to susceptibility to immune dysregulation disorders, with majority found in research on multiple sclerosis (MS) and type 1 diabetes mellitus.[10][11][12][13][14]

IL2RA gene

orthologues with identical protein functionality are relatively abundant and constant among animal species, especially in mammals subgroups. Moreover, conserved homologs of this gene are in mouse, rat, dog, cow, chimpanzee and Rhesus monkey.[15][16]

Expression

CD25 is expressed broadly among

thymocytes, and some myeloid lineage cells (e.g. macrophages, dendritic cells).[17][18] IL2RA has been used as a marker to identify CD4+FoxP3+ regulatory T cells in mice, and it has been found that a large proportion of resting memory T cells constitutively express IL2RA in humans.[19] High expression of CD25 is also found on TCR activated conventional T cells (both CD8+ and CD4+ T lymphocytes), where it is considered to be a marker of T cell activation.[20] Additionally, expression of the IL-2 receptor alpha subunit can be found in non-lymphoid tissues such as lungs (alveolar macrophages), liver (Kupffer cells) and skin (Langerhans cells).[5][18]

IL2RA protein can be expressed in many types of

tumor infiltrating lymphocytes.[21][22]

Structure

Interleukin-2 receptor alpha chain is an

IL2RG) produce a medium-affinity receptor (Kd ~10−9M). Moreover, CD25 is an exclusive subunit that entirely binds IL-2, while CD132 binds the shared γc family cytokines (IL-4, IL-7, IL-9, IL-15 and IL-21), and the CD122 subunit binds also IL-15.[5][23][24]

Soluble IL2RA has been isolated and determined to result from extracellular proteolysis during activation of T lymphocytes.[18] Also, alternately-spliced IL2RA mRNAs have been isolated, but the significance of each is currently unknown.[25]

Signalling cascade of Interleukin-2 Receptor

Th2, Th9, Tfr (T follicular regulatory cells) and suppressing Th17, Tfh ( T follicular helper cells). Additionally, strength of IL-2R signalling in CD8+ T cytotoxic lymphocytes may be connected to phenotypic fate of these cells for effector and memory T cells formation.[5][18][26]

Clinical significance

Roifman's group was the first to identify immunological consequences of CD25 loss and the patient has suffered from

chronic infections and severe autoimmunity resembling Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome, caused by mutations in FOXP3 gene.[23]

CD25 as a biomarker

Levels of CD25 soluble form, called sIL-2Rα, has been connected to pathogenesis of

protozoan Trypanosoma cruzi, patients have increased levels of sIL-2Rα and autoantibodies.[30] In regard to transplantation, higher levels of sCD25 may be used as a predictor of organ rejection and graft-versus-host disease (GVHD) for hematopoietic transplantations. Concerning CVD (cardiovascular diseases) soluble IL-2Rα has positive correlation with hypertension, type 2 diabetes mellitus, cardiac sarcoidosis, stroke and heart failure. For neurological disorders, high levels of sIL-2Rα are a sign for increased risk of developing schizophrenia.[18]

CD25 as a therapeutic target

Since

Fc regions for the purpose of antibody-dependent cell-mediated cytotoxicity, in this case Treg depletion. Antibody marks a cell with IL-2Rα subunit on the surface, which is subsequently recognized and cleared by myeloid cell with Fc receptor.[5] Moreover, for treatment of multiple sclerosis, drug called daclizumab binds to IL2RA and so blocks high-affinity IL-2 receptors on recently activated T cells for interaction with IL-2 as well as IL-2 cross-presentation by dendritic cells.[32][33]

From the other side, treatment strategies for

systemic lupus.[5][6]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000134460 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026770 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^
    S2CID 51939991
    .
  6. ^
    S2CID 250200065
    .
  7. PMID 3925551
    .
  8. ^ a b c "IL2RA Gene - GeneCards | IL2RA Protein | IL2RA Antibody". www.genecards.org. Retrieved 2023-01-25.
  9. ^ a b "UniProt". www.uniprot.org. Retrieved 2023-01-25.
  10. PMID 31242590
    .
  11. doi:10.1016/j.mgene.2020.100750
    .
  12. PMID 17395754
    .
  13. PMID 19956099
    .
  14. S2CID 13940200
    .
  15. ^ "Gene: IL2RA (ENSG00000134460) - Orthologues - Homo_sapiens - Ensembl genome browser 108". www.ensembl.org. Retrieved 2023-01-25.
  16. ^ "IL2RA interleukin 2 receptor subunit alpha [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-01-25.
  17. PMID 30150991
    .
  18. ^
    S2CID 250252097
    .
  19. PMID 30154885
    .
  20. PMID 22120733
    .
  21. PMID 28556984
    .
  22. PMID 15328201
    .
  23. ^
    PMID 23416241
    .
  24. ^
    PMID 35005590
    .
  25. ^ "Entrez Gene: IL2RA interleukin 2 receptor, alpha".
  26. PMID 30619342
    .
  27. ^
    PMID 32619646
    .
  28. PMID 15205267
    .
  29. PMID 33711520
    .
  30. PMID 27242702
    .
  31. PMID 33353953
    .
  32. ^ "Zinbryta Summary of Product Characteristics" (PDF). European Medicines Agency. 2016. Archived from the original (PDF) on 2018-06-14. Retrieved 2016-12-09.
  33. S2CID 32444028
    .

Further reading

External links
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