IL-12 Family
Available Resources for the Study of IL-12 Family
At Creative BioMart, our primary goal is to drive research progress in the field of the IL-12 family. With unwavering dedication, we strive to empower scientists with state-of-the-art tools and expertise related to IL-12 family receptors, ligands, and signaling molecules.
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- Additionally, we provide a wealth of valuable resources to support research efforts in the IL-12 family. These resources include pathways, protein functions, interacting proteins, and other pertinent resource that can significantly augment research outcomes and impact.
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About IL-12 Family
The IL-12 family is a group of cytokines that play important roles in regulating immune responses and inflammation. This family includes IL-12, IL-23, IL-27, and IL-35. Let's explore the ligands, receptors, and related signaling molecules associated with the IL-12 family:
IL-12
Ligands: IL-12 is a heterodimeric cytokine composed of two subunits, p35 and p40. The p35 subunit is unique to IL-12, and the p40 subunit is shared with IL-23. The combination of these subunits forms the IL-12p70 cytokine.
Receptors: IL-12 binds to a receptor complex composed of IL-12 receptor β1 (IL-12Rβ1) and IL-12 receptor β2 (IL-12Rβ2) subunits.
Signaling molecules: Upon IL-12 binding, the associated Janus kinase 2 (JAK2) and Tyrosine kinase 2 (Tyk2) are activated, leading to the phosphorylation of receptor subunits. This activation triggers downstream signaling events, including the activation of signal transducer and activator of transcription 4 (STAT4). Activated STAT4 translocates into the nucleus and promotes the transcription of genes involved in Th1 cell differentiation and activation.
IL-23
Ligands: IL-23 is a heterodimeric cytokine composed of two subunits, p19 and p40. The p19 subunit is unique to IL-23, and the p40 subunit is shared with IL-12. The combination of these subunits forms the IL-23 cytokine.
Receptors: IL-23 binds to a receptor complex consisting of IL-23 receptor (IL-23R) and IL-12 receptor β1 (IL-12Rβ1) subunits.
Signaling molecules: Binding of IL-23 to its receptor complex activates Janus kinase 2 (JAK2) and Tyrosine kinase 2 (Tyk2), leading to the phosphorylation of receptor subunits. This triggers downstream signaling pathways, including the activation of signal transducer and activator of transcription 3 (STAT3). Activated STAT3 translocates into the nucleus and regulates gene expression involved in Th17 cell differentiation and inflammation.
IL-27
Ligands: IL-27 is a heterodimeric cytokine composed of two subunits, p28 and EBI3 (Epstein-Barr virus-induced gene 3).
Receptors: IL-27 binds to a receptor complex consisting of IL-27 receptor α (IL-27Rα) and glycoprotein 130 (gp130) subunits.
Signaling molecules: Binding of IL-27 to its receptor complex activates Janus kinase 1 (JAK1) and Tyrosine kinase 2 (Tyk2). This leads to the phosphorylation of receptor subunits, resulting in the recruitment and activation of signaling molecules such as STAT1 and STAT3. These activated STAT proteins translocate into the nucleus and regulate gene expression involved in various immune responses, including Treg differentiation and the modulation of Th1 and Th17 cell balance.
IL-35
Ligands: IL-35 is a heterodimeric cytokine composed of two subunits, p35 and EBI3 (Epstein-Barr virus-induced gene 3). The p35 subunit is shared with IL-12, while EBI3 is shared with IL-27.
Receptors: IL-35 signals through the IL-12 receptor complex, which includes IL-12 receptor β2 (IL-12Rβ2) and IL-27 receptor α (IL-27Rα) subunits.
Signaling molecules: The specific signaling mechanisms activated by IL-35 are not fully understood. However, it is believed to utilize the JAK/STAT pathway, similar to IL-12 and IL-27.
The IL-12 family and its associated ligands, receptors, and signaling molecules play critical roles in modulating immune responses and maintaining immune homeostasis. Understanding the functions and interactions of these cytokines helps unravel the complex mechanisms of immune regulation and provides potential targets for therapeutic interventions in various immune-related diseases.
Fig.1 IL-12 family cytokines, receptors, and signaling pathways. (Choi J, et al., 2015)
IL-12, IL-23, IL-27, and IL-35 are heterodimeric and share the subunits and their corresponding receptors. Intracellular signaling is mediated by activation of Jak-STAT family
Therapy of IL-12 Family Receptor Activation
Advances in understanding the IL-12 family of cytokines and their receptors have led to the development of therapeutic
- Targeting IL-12/IL-23 Pathway: Ustekinumab is a monoclonal antibody that targets the p40 subunit shared by IL-12 and IL-23. It is approved for the treatment of psoriasis, psoriatic arthritis, and Crohn's disease, effectively blocking IL-12 and IL-23 signaling and reducing inflammation.
- Targeting IL-23 Pathway: Risankizumab is a monoclonal antibody that specifically targets the p19 subunit of IL-23. It is approved for the treatment of moderate to severe plaque psoriasis and has shown promising results in clinical trials for psoriatic arthritis and Crohn's disease.
- Targeting IL-27 Pathway: Emapalumab is a monoclonal antibody that targets the IL-27 receptor (IL-27R) and is approved for the treatment of primary hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune disorder.
- Targeting IL-35 Pathway: Preclinical studies are exploring the potential of using IL-35 as a therapeutic agent. IL-35 administration has shown promising results in suppressing autoimmune responses in experimental models of diseases such as rheumatoid arthritis and graft-versus-host disease.
Fig.2 Cross-regulation of IL-12 family members and their effect on RA pathogenesis. (Choi J, et al., 2015)
Creative BioMart is committed to helping you achieve your scientific goals and make meaningful contributions to the study of the mechanisms of action of the various components of the IL-12 family and their role in disease. Contact us today to learn more about our products and resources.
Related References:
- Choi J, Leung PS, Bowlus C, Gershwin ME. IL-35 and Autoimmunity: a Comprehensive Perspective. Clin Rev Allergy Immunol. 2015;49(3):327-332. doi:10.1007/s12016-015-8468-9
- Pope RM, Shahrara S. Possible roles of IL-12-family cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(4):252-256. doi:10.1038/nrrheum.2012.170
