Immunology · Cytokines and molecules
IL-12 and IL-23 !
- Molecule
IL-12 and IL-23 are sister cytokines from dendritic cells and macrophages: IL-12 creates Th1 cells and IL-23 keeps Th17 cells going.
Updated 2026-11-01
What it is
IL-12 and IL-23 share one subunit, p40; IL-12 adds p35 and IL-23 adds p19. Both are made by dendritic cells and macrophages after they sense microbes through Toll-like and other receptors. IL-12 drives Th1 cells and IFN-γ (key against mycobacteria and Salmonella), whereas IL-23 sustains Th17 cells and IL-17 (key in psoriasis and inflammatory bowel disease).
Step by step
- Dendritic cells and macrophages detect a microbe (for example a mycobacterium).
- They secrete IL-12 (p35+p40) and IL-23 (p19+p40).
- IL-12 binds IL-12Rβ1/β2 on naive CD4 T and NK cells → Th1 differentiation and IFN-γ.
- IFN-γ activates macrophages, which make more IL-12: a positive loop.
- IL-23 binds IL-23R/IL-12Rβ1 on Th17 cells and keeps them producing IL-17.
Clinical notes
- Psoriasis and psoriatic arthritis: ustekinumab and anti-p19 antibodies.
- Crohn disease and ulcerative colitis: ustekinumab and anti-IL-23 antibodies (guselkumab, risankizumab, mirikizumab).
- Mendelian susceptibility to mycobacterial disease: IL12RB1 deficiency is the most common genetic cause; disseminated BCG after vaccination is often the first sign.
- These drugs increase the risk of tuberculosis: latent tuberculosis is screened for before treatment.
Test yourself
Think of the answer, then tap the question to see it.
Which subunit do IL-12 and IL-23 share?
p40; IL-12 also has p35 and IL-23 has p19.
Why does ustekinumab block both IL-12 and IL-23?
It targets the shared p40 subunit, whereas anti-p19 antibodies block only IL-23.
An infant develops disseminated infection after BCG vaccination. Which cytokine axis is suspected?
The IL-12/IFN-γ axis (for example IL12RB1 or IFN-γ receptor deficiency), known as Mendelian susceptibility to mycobacterial disease.
Related
- Cytokines: the table to know
- Interferon-γ
- Interleukin-17
- IL-10 and TGF-β (the brakes)
- Th1, Th2, Th17, Tfh and Treg
- Dendritic cell (professional antigen-presenting cell)
- Granulomatous inflammation
- Phagocyte defects: CGD, LAD, Chédiak–Higashi
Related conditions
Microorganisms
In Pharmacology
Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.
Sources: Major Role of the IL17/23 Axis in Psoriasis Supports the Development of New Targeted Therapies (Frontiers in Immunology, 2021); Overview of Mendelian Susceptibility to Mycobacterial Diseases (MSMD) (Cureus (PubMed Central), 2025); Ustekinumab Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Th17/Treg imbalance in inflammatory bowel disease: immunological mechanisms and microbiota-driven regulation (Frontiers in Immunology, 2025).
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Representative model, for educational purposes only.