Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
Abstract
Severe combined immunodeficiency (SCID) is caused by multiple genetic defects. The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref. 4), which encodes the common cytokine receptor gamma chain (gamma(c)) that is shared by the IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. In XSCID and SCID resulting from mutations in JAK3, which encodes a Janus family tyrosine kinase that couples to gamma(c) and is required for gamma(c)-dependent signalling, T- and natural killer (NK)-cells are decreased but B-cell numbers are normal (T(-)B(+)NK(-)SCID). Some SCID patients lack T cells but retain NK cells. Given diminished T-cell development in Il7- or Il7r-deficient mice and that Il/7r-deficient mice have NK cells, we hypothesized that T(-)B(+)NK(+) SCID might result from defective IL-7 signalling, although apparent differences in the role of the IL-7/IL-7R pathway in humans and mice in T-cell and B-cell development have been suggested. We now demonstrate that defective IL7R expression causes T(-)B(+)NK(+) SCID, indicating that the T-cell, but not the NK-cell, defect in XSCID results from inactivation of IL-7Ralpha signalling.
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Mutations in the IL-7Rα or γc in humans lead to severe combined immunodeficiency, confirming the importance of the IL-7 signaling pathway in the development of T cells.
“Mutations in the IL-7Rα or γc in humans lead to severe combined immunodeficiency, confirming the importance of the IL-7 signaling pathway in the development of T cells (158, 159).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [158]
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- Authors
- Puel, A., Ziegler, S. F., Buckley, R. H., & Leonard., W. J.
- Affiliations
- National Institutes of Health (US)
- Duke University (US)
- Venue
- Nature Genetics
- Published
- 1998-12
- Volume
- 20
- Issue
- 4
- Pages
- 394-397
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- DOI
- 10.1038/3877
- OpenAlex
- W1509163238
- Cited by
- 813
- References
- 29
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 20 · 2022: 22 · 2021: 24 · 2020: 24 · 2019: 28 · 2018: 26 · 2017: 22 · 2016: 31 · 2015: 35 · 2014: 30 · 2013: 37 · 2012: 57
- FWCI
- 9.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- severe combined immunodeficiency, X-linked SCID, CD127, T cell development, natural killer cells, B cells, JAK3, IL2RG
- MeSH terms
- Animals, B-Lymphocytes, Base Sequence, Humans, Infant, Infant, Newborn, Killer Cells, Natural, Molecular Sequence Data, T-Lymphocytes, Signal Transduction, Polymerase Chain Reaction, Mutagenesis, Site-Directed, Severe Combined Immunodeficiency, DNA Primers, Receptors, Interleukin-7, Mice
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