Myeloid IPMK promotes the resolution of serum transfer-induced arthritis in mice

Abstract

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.

Suppressive effects of (-)-tubaic acid on RANKL-induced osteoclast differentiation and bone resorption

“…Osteoclasts were generated from bone marrow-derived macrophages (BMMs) as previously described (Ihn et al 2019 ; Ihn et al 2019 ; Ahn et al 2021 ). Bone marrow cells obtained from 6–8-week-old C57BL/6 mice (Dae Han Bio Link, Chungbuk, Korea) were incubated in α-MEM containing 10% FBS for 24 h, and nonadherent cells were incubated in the presence of 30 ng/ml M-CSF for three days to generate BMMs.…”

Deletion of IP6K1 in mice accelerates tumor growth by dysregulating the tumor-immune microenvironment

“…Bone marrow-derived macrophages (BMDMs) were isolated from mouse femurs and tibias and differentiated for 6 days on petri dishes in BMDM medium [RPMI 1640, 10% FBS, recombinant M-CSF (30 ng/mL), 1 mM sodium pyruvate, 2 mM L-glutamine, penicillin/streptomycin (100 μg/mL)]. Adherent BMDMs were detached on day 6, plated 6-well culture plates (10 6 cells/well) (Kim et al 2017 ; Ahn et al 2021 ). For M1/M2 polarization experiments, BMDMs were stimulated with LPS (100 ng/mL) and IFN-γ (10 ng/mL) for M1, and IL-4 (20 ng/mL) for M2 for 24 hours and analyzed for gene and protein expression.…”

Effect of TRAF6 -knockout on gene expression and lncRNA expression in Epithelioma papulosum cyprini (EPC) cells

“…For example, TLR1, TLR2, and TLR6 identify lipids, while, TLR7, TLR8 and TLR9 recognize nucleic acids. Once TLRs are triggered, myeloid differentiation factor 88 (MyD88)-dependent or MyD88-independent pathways are activated, recruiting tumor necrosis factor receptor-associated factor 6 ( TRAF6 ) (Rauta et al 2014 ; Ahn et al 2021 ).…”