Interleukin 12

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Interleukin-12
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Human Interleukin 12
Crystal structure of human IL-12 (red helices)
Identifiers
SymbolIL12, p70
PDB1F45
Chr. 3 p12-q13.2
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StructuresSwiss-model
DomainsInterPro
Chr. 5 q31.1-33.1
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StructuresSwiss-model
DomainsInterPro

Interleukin 12 (IL-12) is an

heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35.[2]
Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

Gene and structure

IL12 is a

IL12B has three beta sheet
domains.

Functions

IL-12 is involved in the differentiation of naive

, which is associated with IL-12 activity.

IL-12 plays an important role in the activities of

IFN-γ
production and killing of target cells.

IL-12 also has anti-

tumors tested to this date. There is a link that may be useful in treatment between IL-12 and the diseases psoriasis & inflammatory bowel disease.[citation needed] There has also been research indicating that interleukin 12 is linked with interleukin 23 and antibodies against these factors have a possible role in creating an anti-inflammatory effect in inflammatory bowel disease. [5]

Signal transduction

IL-12 binds to the IL-12 receptor, which is a heterodimeric receptor formed by

An extensive review and visualization of IL-12 signaling can be found at the peer-reviewed pathway database Reactome: Interleukin-12 family

Autoimmunity

IL-12 is linked with

gene knock-out
in mice or a treatment of mice with IL-12 specific antibodies ameliorated the disease.

Results published in the Journal of Allergy and Clinical Immunology from a study where mice that were bred to be allergic to peanuts, interleukin-12 has been shown to not be present, suggesting that the molecule normally stops allergies to food from developing. Further investigation is underway, to determine whether the results found in mice are as profound in humans.[8][9]

IL-12 and IL-12 receptor β1 mutations

Interleukin 12 (IL-12) is produced by activated antigen-presenting cells (

NK cells.[11]

A child with

homozygous deletion within the IL-12 p40 subunit gene, precluding expression of functional IL-12 p70 cytokine by activated dendritic cells and phagocytes. As a result, IFNγ production by the child's lymphocytes was markedly impaired.[12]
This suggested that IL-12 is essential for protective immunity to intracellular bacteria such as .

Support is lent to this idea by the observation that a

premature stop codons
in the extracellular domain, resulting in unresponsiveness to this cytokine, again demonstrating IL-12's crucial role in host defense.

Defective Th1 and Th17 immune responses leading to

Jak2 and Tyk2 activity.[13]

See also

  • CNTO 1275

References

Further reading