IL-23A

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 8, 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 IL23A mouse model

We have developed and characterized transgenic mice expressing in a dysregulated manner the human IL23A (IL23p19).  In this line, dysregulation 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 is the gene’s  own promoter. TghIL23A mice develop a lupus-like autoimmune pathology and are available for testing therapeutics.

Preclinical Platform for the evaluation of IL23A targeting therapeutics

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TghIL23A

A humanised mouse model that overexpresses human IL23A and develops a chronic autoimmune pathology with cutaneous lesions and renal dysfunction.

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