IL-12B

The Interleukin 23 (IL-23) cytokine is a heterodimeric cytokine consisting of the two subunits p19 and p40. It is an inducer of the Th17 cell population and a component of the IL-23/IL-17 immune pathway which is an orchestrator of many pathological conditions, including psoriasis.
pleiotropic cytokine

Date:

March 9, 2024

Category:

IL23 as a therapeutic target

Due to its crucial role in pathogenesis, the two IL-23 subunits are promising therapeutic targets for inflammatory conditions. The first approved biologic agent targeting IL-23 was ustekinumab (Stelara), a fully human monoclonal antibody against the shared IL-12/IL23 p40 subunit that was approved for the indication of psoriasis and Chron’s disease. Guselkumab (Tremfya), a monoclonal antibody targeting the IL23p19 subunit was recently approved for the treatment of psoriasis, while tildrakizumab (Ilumya), also targeting IL23p19, and other therapeutics are currently under development.

The humanized IL12p40 mouse model

We have developed and characterized transgenic mice expressing in a dysregulated manner the human IL23/IL12p40 subunit. Dysregulated expression is the result of the replacement of the gene’s 3’UTR with that of beta globin that is not subject to posttranscriptional regulation. Expression pattern is determined by the promoter used, that in this case is the  human keratin 14 promoter. TgK14hIL12B mice develop lupus-like autoimmune pathology.

Preclinical Platforms for the evaluation of TNF targeting therapeutics

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TgK14hIL12B

A humanised mouse model that overexpresses human IL23/IL12B and develops a chronic autoimmune pathology with cutaneous lesions and renal dysfunction.

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