Colitis / Intestinal Inflammation & Interleukin-10 (IL-10)

Previous studies show that Toll-Like Receptors (TLRs) signals change macrophage lipids (Macrophages (CD68s) & Toll-like receptor 2 (TLR-2)). This affects their function. Interleukin-10 (IL-10) is made after some Toll-Like Receptors (TLRs) are activated. It helps resolve inflammation. Interleukin-10 (IL-10) signalling led to more ceramides and modified ceramides. There was also a decrease in sphingomyelins.
York et al. 2024 Nature 627: 628-635

Interleukin-10 (IL-10) signalling regulates sphingolipid metabolism. This occurs in macrophages downstream of toll-like receptor 2 (TLR2). Without Interleukin-10 (IL-10), Toll-like receptor 2 (TLR-2)-activated macrophages increase metabolic flux. This happens through the de novo sphingolipid biosynthesis pathway. It leads to the accumulation of ceramides. Increased saturated very-long-chain (VLC) ceramides contribute to inflammation. This is true both in vitro and in vivo. Altered sphingolipid metabolism in IL-10 deficient cells is due to reduced MUFA synthesis. Providing exogenous MUFAs corrects this. Prolonged inflammatory gene expression is enforced by altered VLC ceramide homeostasis. It requires the NFKB family transcription factor REL. These studies show IL-10's role in lipid metabolism regulation. It is necessary to control REL-dependent inflammation. Targeting lipid homeostasis in the intestine could manage IBD-related inflammation
York et al. 2024 Nature 627: 628-635

The mechanism of IL-10–IL-10R signalling is unclear. It reduces inflammation. Inflammatory signals change lipid metabolism in immune cells. This supports inflammation and effector functions. The hypothesis is that IL-10 may alter lipid metabolism. This counters inflammatory stimuli.
Reboldi et al. 2014 Science 345: 679-684
Kelly & O’Neill 2015 Cell Res 25: 771-784
York et al. 2015 Cell 163: 1716-1729
Apostolidis et al. 2016 Nat Immunol 17: 556-564
O'Neill & Pearce 2016 J. Exp. Med. 213: 15-23
Dang et al. 2017 Cell 171: 1057-1071
Hsieh et al. 2020b Cell Metab 32: 128-143
Mukhopadhyay et al. 2020 J Exp Med 217: e20180649
Zhou et al. 2020c Nat Immunol 21: 746-755

IL-10 signalling is crucial. It modulates mucosal inflammation in the intestine. Deleting IL-10 or its receptor (IL-10R) causes severe inflammatory bowel disease (IBD). This occurs in both mice and humans
Groux & Cottrez 2003 J Autoimmun 20: 281-285
Glocker et al. 2011 Ann NY Acad Sci 1246: 102-107
Li et al. 2014 Mucosal Immunol 7: 869-878
Zhu et al. 2017 Gastroenterology Res 10: 65-69

IL-10 is an anti-inflammatory cytokine. It limits immune activation. It affects both innate and adaptive immune cells
Saraiva & O’Garra 2010 Nat Rev Immunol 10: 170-181

IL-10-producing CD4 cells suppress colitis
Mazmanian et al. 2008

see also:
AIM2 inflammasome
Biosynthesis & Cholesterol
Immune cell metabolism / Immunometabolism
Inflammatory Bowel Disease (IBD) & Interleukin-10 (IL-10)
Interleukin-10 (IL-10)
Interferons Type I (IFN Type I) & NFKB Signal transduction / NFKB Signal transduction pathway
Oxysterols
Protein Phosphatase 2A (PP2A)
Regulatory T Cells (Tregs)
Self antigens / Autoantigens / Autoimmunity
Sphingolipids
Toll-Like Receptors (TLRs)
XXX - Bifidobacterium bifidum 231 & Trinitrobenzolsulfonsäure (TNBS) colitis