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
. 2019 Jan;244(1):42-51.
doi: 10.1177/1535370218824547. Epub 2019 Jan 21.

IL-12 and IL-23/Th17 axis in systemic lupus erythematosus

Maddalena Larosa  1 , Margherita Zen  1 , Mariele Gatto  1 , Diogo Jesus  2 , Elisabetta Zanatta  1 , Luca Iaccarino  1 , Luis Inês  2   3   4 , Andrea Doria  1
Affiliations
Review

IL-12 and IL-23/Th17 axis in systemic lupus erythematosus

Maddalena Larosa et al. Exp Biol Med (Maywood). 2019 Jan.

Abstract

Our article is focused on emerging pathogenetic pathways in systemic lupus erythematosus (SLE). Notably, IL-12 and IL-23 have been described as emerging cytokines in SLE pathogenesis. We know that IL-23 stimulates Th17 cells to produce IL-17. We try to point out the importance of IL-23/Th17 axis in SLE and to focus on the interaction between this axis and IL-12. Ustekinumab, a fully human IgG1κ monoclonal antibody directed towards the p40 shared subunit of IL-12 and IL-23, has been recently investigated in SLE, suggesting a potential novel therapeutic strategy in SLE. To our knowledge, there are no reviews which simultaneously focus on IL-12 an IL-23/Th17 axis in SLE. Thus, we believe our work will be of interest to the readers.

Keywords: IL-12; IL-23/Th17 axis; SLE; Th1 response; immune response; ustekinumab.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Once secreted by DCs, macrophages, and monocytes, IL-12 targets different cell clusters. It regulates the proliferation of T lymphocytes and it stimulates B cells in producing auto-antibodies. IL-12 plays a crucial role also in microbial response, by targeting NK cells. This cytokine is linked to the IL-23/Th17 axis. APCs release IL-23 and IL-17. IL-23 inhibitis IL-2 production and is fundamental for Th differentiation into Th17. These lymphocytes release IL-17, which target endothelial cells, macrophages, fibroblasts, and keratinocytes provoking tissue inflammation. (A color version of this figure is available in the online journal.) IL-12: interleukin-12; IL-23: interleukin-23; IL-17: interleukin 17; IL-2: interleukin 2; NK: natural killer; APC: antigen presenting cell; Th1: T helper 1; Treg: T regulatory cell; Th17: T Helper 17; IL-12R: IL-12 Receptor; IL-23R: IL-23 receptor.
See this image and copyright information in PMC

References

    1. Gatto M, Zen M, Ghirardello A, Bettio S, Bassi N, Iaccarino L, Punzi L, Doria A. Emerging and critical issues in the pathogenesis of lupus. Autoimmun Rev 2013; 12:523–36 - PubMed
    1. Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR. Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41:1241–50 - PubMed
    1. Ramani K, Biswas PS. Interleukin 17 signaling drives Type I interferon induced proliferative crescentic glomerulonephritis in lupus-prone mice. Clin Immunol 2016; 162:31–6 - PubMed
    1. La Paglia GMC, Leone MC, Lepri G, Vagelli R, Valentini E, Alunno A, Tani C. One year in review 2017: systemic lupus erythematosus. Clin Exp Rheumatol 2017; 35:551–61 - PubMed
    1. Becher B, Durell BG, Noelle RJ. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest 2002; 110:4939–7 - PMC - PubMed

MeSH terms