Myeloid IPMK Promotes the Resolution of Serum Transfer-Induced Arthritis in Mice
Open accessAbstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by widespread joint inflammation, which leads to joint damage, disability, and mortality. Among the several types of immune cells, myeloid cells such as macrophages are critical for controlling the pathogenesis of RA. Inositol phosphates are water-soluble signaling molecules, which are synthesized by a series of enzymes including inositol phosphate kinases. Previous studies revealed actions of inositol phosphates and their metabolic enzymes in the modulation of inflammation such as Toll-like receptor-triggered innate immunity. However, the physiological roles of inositol polyphosphate (IP) metabolism in the regulation of RA remain largely uncharacterized. Therefore, our study sought to determine the role of inositol polyphosphate multikinase (IPMK), a key enzyme for IP metabolism and various cellular signaling control mechanisms, in mediating RA. Using myeloid cell-specific IPMK knockout (KO) mice, arthritis was induced via intraperitoneal K/BxN serum injection, after which disease severity was evaluated. Both wild-type and IPMK KO mice developed similar RA phenotypes; however, conditional deletion of IPMK in myeloid cells led to elevated arthritis scores during the resolution phase, suggesting that IPMK deficiency in myeloid cells impairs the resolution of inflammation. Bone marrow-derived IPMK KO macrophages exhibited no apparent defects in immunoglobulin Fc receptor (FcR) activation, osteoclast differentiation, or resolvin signaling. Taken together, our findings suggest that myeloid IPMK is a key determinant of RA resolution.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
IPMK is implicated in neurodegeneration, cancer, and inflammation.
“Over two decades, multidisciplinary research has unveiled its far-reaching biological roles and implications in diverse diseases, including neurodegeneration, cancer, and inflammation.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [28]
The Discussion reports an association involving IPMK, Alzheimer’s disease, and immune-mediated diseases, while the paper’s findings concern resolution of inflammatory arthritis in mice. The Introduction also describes IPMK’s broad signaling roles. Neither section establishes an implication in cancer; the mentions of p53 and cancer in the Introduction and References do not support that part of the claim. Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIPMK is involved in inflammatory disorders, obesity, Alzheimer's disease, inflammatory bowel disease, and intestinal neuroendocrine tumors.
“Over the past two decades, research utilizing animal models and human mutation analyses has revealed IPMK’s involvement in a wide array of human diseases, including inflammatory disorders [28,29], obesity [30,31], Alzheimer’s disease [32], inflammatory bowel disease [33,34], and intestinal neuroendocrine tumors [35].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [28]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment
Schett, G., & Gravallese, E. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.153 · Cited by 947 · see citing works
Association between genetic traits for immune-mediated diseases and Alzheimer disease
Yokoyama, J. S., Wang, Y., Schork, A. J., Thompson, W. K., Karch, C. M., Cruchaga, C., McEvoy, L. K., Witoelar, A., Chen, C.-H., Holland, D., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0150 · Cited by 176 · see citing works
Flagged first, then by citations
Research works printed but not linked: 29
- Bang S, Chen Y, Ahima RS, Kim SF. 2014. Convergence of IPMK and LKB1-AMPK signaling pathways on metformin action. Mol Endocrinol. 28(7): 1186– 1193. doi: 10.1210/me.2014-1134. 24877601 PMC4075158 · DOI · Paper page
- Bang S, Kim S, Dailey MJ, Chen Y, Moran TH, Snyder SH, Kim SF. 2012. AMP-activated protein kinase is physiologically regulated by inositol polyphosphate multikinase. Proc Natl Acad Sci USA. 109(2): 616– 620. doi: 10.1073/pnas.1119751109. 22203993 PMC3258619 · DOI
- Brennan FM, McInnes IB. 2008. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 118(11): 3537– 3545. doi: 10.1172/JCI36389. 18982160 PMC2575731 · DOI
- Cai Z, He S, Li T, Zhao L, Zhang K. 2020. Plumbagin inhibits proliferation and promotes apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inactivating PI3K/Akt/MTOR pathway. Anim Cells Syst. 24(4): 197– 204. doi: 10.1080/19768354.2020.1790416. PMC7473319 33029296 · DOI
- Chakraborty A, Kim S, Snyder SH. 2011. Inositol pyrophosphates as mammalian cell signals. Sci Signal. 4(188): 1– 12. doi: 10.1126/scisignal.2001958. PMC3667551 21878680 · DOI · Paper page
- Christensen AD, Haase C, Cook AD, Hamilton JA. 2016. K/BxN serum-transfer arthritis as a model for human inflammatory arthritis. Front Immunol. doi: 10.3389/fimmu.2016.00213. PMC4889615 27313578 · DOI
- Fullerton JN, Gilroy DW. 2016. Resolution of inflammation: a new therapeutic frontier. Nat Rev Drug Discovery. 15(8): 551– 567. doi: 10.1038/nrd.2016.39. 27020098 · DOI · Paper page
- González-Chávez SA, Quiñonez-Flores CM, Espino-Solís GP, Vázquez-Contreras JÁ, Pacheco-Tena C. 2019. Exercise exacerbates the transcriptional profile of hypoxia, oxidative stress and inflammation in rats with adjuvant-induced arthritis. Cells. doi: 10.3390/cells8121493. PMC6952786 31766745 · DOI
- Kim E, Beon J, Lee S, Park SJ, Ahn H, Kim MG, Park JE, et al. 2017. Inositol polyphosphate multikinase promotes toll-like receptor–induced inflammation by stabilizing TRAF6. Sci Adv. 3(4): e1602296. doi: 10.1126/sciadv.1602296. 28439546 PMC5400429 · DOI · Paper page
- Kim S, Kim SF, Maag D, Maxwell MJ, Resnick AC, Juluri KR, Chakraborty A, et al. 2011. Amino acid signaling to MTOR Mediated by inositol polyphosphate multikinase. Cell Metab. 13(2): 215– 221. doi: 10.1016/j.cmet.2011.01.007. 21284988 PMC3042716 · DOI · Paper page
- Kim E, Tyagi R, Lee J-Y, Park J, Kim Y-r, Beon J, Chen PY, Cha JY, Snyder SH, Kim S. 2013. Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes. Proc Natl Acad Sci USA. 110(49): 19938– 19943. doi: 10.1073/pnas.1320171110. 24248338 PMC3856792 · DOI · Paper page
- Lee S, Beon J, Kim M-G, Kim S. 2020. Inositol polyphosphate multikinase in adipocytes is dispensable for regulating energy metabolism and whole body metabolic homeostasis. Am J Physiol Endocrinol Metab. 319(2): E401– E409. doi: 10.1152/ajpendo.00030.2020. 32634320 · DOI · Paper page
- Lee S, Kim M-G, Ahn H, Kim S. 2020. Inositol pyrophosphates: signaling molecules with pleiotropic actions in mammals. Molecules. doi: 10.3390/molecules25092208. PMC7249018 32397291 · DOI
- Lee H, Kim W, Kang H-G, Kim W-J, Lee SC, Kim S-J. 2020. Geranium thunbergii extract-induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. Anim Cells Syst. 24(1): 26– 33. doi: 10.1080/19768354.2019.1699161. PMC7048224 32158613 · DOI
- Lee B, Park SJ, Hong S, Kim K, Kim S. 2021. Inositol polyphosphate multikinase signaling: multifaceted functions in health and disease. Mol Cells. 44(4): 187– 194. doi: 10.14348/molcells.2021.0045. 33935040 PMC8112168 · DOI
- McInnes IB, Schett G. 2011. The pathogenesis of rheumatoid arthritis. N Engl J Med. 365(23): 2205– 2219. doi: 10.1056/NEJMra1004965. 22150039 · DOI · Paper page
- Norling LV, Perretti M. 2013. The role of omega-3 derived resolvins in arthritis. Curr Opin Pharmacol. 13(3): 476– 481. doi: 10.1016/j.coph.2013.02.003. 23434193 · DOI
- Paniagua RT, Chang A, Mariano MM, Stein EA, Wang Q, Lindstrom TM, Sharpe O, et al. 2010. C-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis. Arth Res Therapy. 12(1): 1– 15. doi: 10.1186/ar2940. PMC2875666 20181277 · DOI
- Park SJ, Lee S, Park SE, Kim S. 2018. Inositol pyrophosphates as multifaceted metabolites in the regulation of mammalian signaling networks. Anim Cells Syst. 22(1): 1– 6. doi: 10.1080/19768354.2017.1408684. · DOI
- Sánchez-Mejorada G, Rosales C. 1998. Signal transduction by immunoglobulin Fc receptors. J Leukocyte Biol. 63(5): 521– 533. doi: 10.1002/jlb.63.5.521. 9581795 · DOI
- Schett G, Neurath MF. 2018. Resolution of chronic inflammatory disease: universal and tissue-specific concepts. Nat Commun. 9(1): 3261. doi: 10.1038/s41467-018-05800-6. 30111884 PMC6093916 · DOI
- Serhan CN, Levy BD. 2018. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest. doi: 10.1172/JCI97943. PMC6025982 29757195 · DOI · Paper page
- Serhan CN, Savill J. 2005. Resolution of inflammation: the beginning programs the end. Nat Immunol. 6(12): 1191– 1197. doi: 10.1038/ni1276. 16369558 · DOI · Paper page
- Siouti E, Andreakos E. 2019. The many facets of macrophages in rheumatoid arthritis. Biochem Pharmacol. 165: 152– 169. doi: 10.1016/j.bcp.2019.03.029. 30910693 · DOI
- Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, et al. 2018. Rheumatoid arthritis. Nat Rev Dis Prim. 4(1): 18001. doi: 10.1038/nrdp.2018.1. 29417936 · DOI
- Song JJ, Hwang I, Cho KH, Garcia MA, Kim AJ, Wang TH, Lindstrom TM, et al. 2011. Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis. J Clin Invest. 121(9): 3517– 3527. doi: 10.1172/JCI46387. 21804193 PMC3163960 · DOI
- Watanabe S, Alexander M, Misharin AV, Scott Budinger GR. 2019. The role of macrophages in the resolution of inflammation. J Clin Invest. 129(7): 2619– 2628. doi: 10.1172/JCI124615. 31107246 PMC6597225 · DOI · Paper page
- Xu R, Sen N, Paul BD, Snowman AM, Rao F, Scott Vandiver M, Xu J, Snyder SH. 2013. Inositol polyphosphate multikinase is a coactivator of P53-mediated transcription and cell death. Sci Signal. 6(269): ra22. doi: 10.1126/scisignal.2003405. 23550211 PMC4108196 · DOI · Paper page
- Zhang Y, Yang K, Yang J, Lao Y, Deng L, Deng G, Yi J, Sun X, Wang Q. 2020. SENP3 suppresses osteoclastogenesis by de-conjugating SUMO2/3 from IRF8 in bone marrow-derived monocytes. Cell Rep. 30(6): 1951– 1963. doi: 10.1016/j.celrep.2020.01.036. 32049023 · DOI
Cited by
Sorted by citations
From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease
Mishra, S. H., Chatterjee, S., Viera-Preval, L., & Guha, P. (2025) · Biomolecules · doi:10.3390/biom15091266 · Cited by 1 · see citing works
“…research utilizing animal models and human mutation analyses has revealed IPMK’s involvement in a wide array of human diseases, including inflammatory disorders [28,29], obesity [30,31], Alzheimer’s disease [32], inflammatory bowel disease [33,34], and intestinal neuroendocrine tumors [35].”
Influential
- Authors
- Ahn, H., Roh, J. S., Lee, S., Beon, J., Lee, B., Sohn, D. H., & Kim, S.
- Affiliations
- Korea Advanced Institute of Science and Technology (KR)
- Daegu Haany University (KR)
- Pusan National University (KR)
- Corresponding author
- Sohn, Dong Hyun
- Kim, Seyun
- Venue
- Animal Cells and Systems
- Publisher
- Informa UK Limited
- Published
- 2021-07-04
- Volume
- 25
- Issue
- 4
- Pages
- 219-226
- ISSN
- 1976-8354 (ISSN-L)
- 2151-2485
- PMC
- PMC8366620
- OpenAlex
- W3180392696
- Cited by
- 9
- References
- 2
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Animal Cells and Systems (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation of Korea (NRF-2018R1A2B2005913, NRF-2018R1A5A1024261, NRF-2018R1A5A2023879, NRF-2020R1A2C3005765)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- rheumatoid arthritis, inositol polyphosphate multikinase, myeloid cells, macrophages, inflammation resolution, inositol phosphate metabolism, conditional knockout mice, osteoclastogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
