The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages
Open accessAbstract
The Krebs cycle-derived metabolite itaconate and its derivatives suppress the inflammatory response in pro-inflammatory "M1" macrophages. However, alternatively activated "M2" macrophages can take up itaconate. We therefore examined the effect of itaconate and 4-octyl itaconate (OI) on M2 macrophage activation. We demonstrate that itaconate and OI inhibit M2 polarization and metabolic remodeling. Examination of IL-4 signaling revealed inhibition of JAK1 and STAT6 phosphorylation by both itaconate and OI. JAK1 activation was also inhibited by OI in response to IL-13, interferon-β, and interferon-γ in macrophages and in T helper 2 (Th2) cells. Importantly, JAK1 was directly modified by itaconate derivatives at multiple residues, including cysteines 715, 816, 943, and 1130. Itaconate and OI also inhibited JAK1 kinase activity. Finally, OI treatment suppressed M2 macrophage polarization and JAK1 phosphorylation in vivo. We therefore identify itaconate and OI as JAK1 inhibitors, suggesting a new strategy to inhibit JAK1 in M2 macrophage-driven diseases.
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Cites
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Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
Mills, E. L., Ryan, D. G., Prag, H. A., Dikovskaya, D., Menon, D., Zaslona, Z., Jedrychowski, M. P., Costa, A. S. H., Higgins, M., Hams, E., et al. (2018) · Nature · doi:10.1038/nature25986 · Cited by 1,885
Self-citationNrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
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Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer
Xue, C., Yao, Q., Gu, X., Shi, Q., Yuan, X., Chu, Q., Bao, Z., Lu, J., & Li, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01468-7 · Cited by 699
Metabolism, metabolites, and macrophages in cancer
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Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective
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4-octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING
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Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses
Lesbats, J., Brillac, A., Reisz, J. A., Mukherjee, P., Lhuissier, C., Fernández-Monreal, M., Dupuy, J.-W., Sequeira, A., Tioli, G., De La Calle Arregui, C., et al. (2025) · Nature · doi:10.1038/s41586-025-08629-4 · Cited by 74
Metadata
- Authors
- Runtsch, M. C., Angiari, S., Hooftman, A., Wadhwa, R., Zhang, Y., Zheng, Y., Spina, J. S., Ruzek, M. C., Argiriadi, M. A., McGettrick, A. F., Mendez, R. S., Zotta, A., Peace, C. G., Walsh, A., Chirillo, R., Hams, E., Fallon, P. G., Jayaraman, R., Dua, K., Brown, A. C., Kim, R. Y., Horvat, J. C., Hansbro, P. M., Wang, C., & O’Neill, L. A. J.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 34
- Issue
- 3
- Pages
- 487-501.e8
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W4214769648
- Cited by
- 323
- References
- 62
- FWCI
- 20.49
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Runtsch, M. C., Angiari, S., Hooftman, A., Wadhwa, R., Zhang, Y., Zheng, Y., Spina, J. S., Ruzek, M. C., Argiriadi, M. A., McGettrick, A. F., Mendez, R. S., Zotta, A., Peace, C. G., Walsh, A., Chirillo, R., Hams, E., Fallon, P. G., Jayaraman, R., Dua, K., . . . O’Neill, L. A. J. (2022). Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages. Cell Metabolism. https://doi.org/10.1016/j.cmet.2022.02.002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
