Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Oct;51(1):5-14.
doi: 10.1007/s12026-011-8209-y.

Molecular interactions within the IL-6/IL-12 cytokine/receptor superfamily

Lindsay L Jones  1 , Dario A A Vignali
Affiliations
Review

Molecular interactions within the IL-6/IL-12 cytokine/receptor superfamily

Lindsay L Jones et al. Immunol Res. 2011 Oct.

Abstract

Production of cytokines by immune cells in response to stimuli and the binding of cytokines to specific receptors on target cells is a central feature of the immune response. The IL-12 cytokine family is particularly influential in determining the fate of T cells and is characterized by the sharing of cytokine and receptor subunits. A thorough understanding of the molecular interactions within this family will be a key to the development of therapeutic inhibitors or enhancers of IL-12 family function. While the current structural and molecular data for IL-12 family members is limited, there is ample information on the structurally related IL-6 cytokine family. This review will summarize the current structural and mutagenesis data within the IL-12 family and will attempt to utilize similarities between the IL-6 and IL-12 families to understand molecular interactions between IL-12 family subunits and with receptor components.

PubMed Disclaimer

Figures

Fig 1
Fig 1
IL-12 family cytokines and their receptors IL-12 is formed by p40 and p35 and signals through IL-12Rb1 and IL-12Rb2. IL-23 is formed from p19 and p40 and signals through IL-12Rb1 and IL-23R. IL-27 is formed by p28 and Ebi3 and signals through WSX-1 and gp130. IL-35 is formed from p35 and Ebi3. No receptor for IL-35 has been described to date. Modular representations of IL-12 family members and receptors were modified from [30].
Fig 2
Fig 2
Predicted site 1, site 2 and site 3 interactions within IL-12 family complexes. Site 1, site 2 and site 3 interactions between some IL-12 family members and their receptor complexes have been previously predicted based on IL-6 and LIF complex crystal structures [30]. Site 1 is formed by the interface between the alpha and beta subunits of the heterodimeric cytokine. The cytokine-binding homology region of a receptor subunit binds to the cytokine forming site 2. The immunoglobulin domain of a second receptor subunit interacts with the tip of the alpha subunit, forming site 3.
See this image and copyright information in PMC

References

    1. Gee K, Guzzo C, Che Mat NF, Ma W, Kumar A. The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets. 2009;8:40–52. - PubMed
    1. Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol. 1998;16:495–521. - PubMed
    1. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–25. - PubMed
    1. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910–4. - PubMed
    1. Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, Churakova T, Travis M, Vaisberg E, Blumenschein WM, Mattson JD, Wagner JL, To W, Zurawski S, McClanahan TK, Gorman DM, Bazan JF, de Waal Malefyt R, Rennick D, Kastelein RA. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity. 2002;16:779–90. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources