2019 Feb 15
Institute for Medical Microbiology and Hygiene, Philipps-University Marburg, Germany
The short-chain fatty acid pentanoate suppresses autoimmunity by modulating the metabolic-epigenetic crosstalk in lymphocytes.
PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377655/
Abstract
Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this reprogramming is mediated by supplying additional pentanoate-originated acetyl-CoA for histone acetyltransferases, and by pentanoate-triggered enhancement of mTOR activity. In experimental mouse models of colitis and multiple sclerosis, pentanoate-induced regulatory B cells mediate protection from autoimmune pathology. Additionally, pentanoate shows a potent histone deacetylase-inhibitory activity in CD4+ T cells, thereby reducing their IL-17A production. In germ-free mice mono-colonized with segmented filamentous bacteria (SFB), pentanoate inhibits the generation of small-intestinal Th17 cells and ameliorates SFB-promoted inflammation in the central nervous system. Taken together, by enhancing IL-10 production and suppressing Th17 cells, the SCFA pentanoate might be of therapeutic relevance for inflammatory and autoimmune diseases.
SCFAs
SCFAs
https://www.eboro.cz
Re: SCFAs
2019 Jun 20
Department of Comparative Pathobiology, Purdue University, West Lafayette
Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586800/
Abstract
Microbial metabolites, produced in the intestine, have significant effects on inflammatory diseases throughout the body. Short-chain fatty acids (SCFAs) have protective effects on experimental autoimmune encephalitis (EAE) responses but the detailed roles of SCFAs and their receptors in regulating autoimmune CNS inflammation have been unclear. SCFAs metabolically regulate T cells and change the phenotype of antigen presenting cells to efficiently induce IL-10+ regulatory T cells. In line with the overall protective effect, blood levels of major SCFAs, such as acetate, propionate and butyrate, are significantly decreased in long-term active progressive multiple sclerosis (MS) patients. Importantly, SCFAs can induce CD4+ effector T cells, which are highly inflammatory when transferred into mice, suggesting that the direct effect of SCFAs on T cells can even be pro-inflammatory in the CNS. In contrast to the moderate protective effect of SCFAs, mice deficient in GPR41 or GPR43 are more resistant to EAE pathogenesis. Thus, despite the overall protective function of SCFAs, SCFAs and their receptors have the potential to regulate autoimmune CNS inflammation both positively and negatively.
Department of Comparative Pathobiology, Purdue University, West Lafayette
Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586800/
Abstract
Microbial metabolites, produced in the intestine, have significant effects on inflammatory diseases throughout the body. Short-chain fatty acids (SCFAs) have protective effects on experimental autoimmune encephalitis (EAE) responses but the detailed roles of SCFAs and their receptors in regulating autoimmune CNS inflammation have been unclear. SCFAs metabolically regulate T cells and change the phenotype of antigen presenting cells to efficiently induce IL-10+ regulatory T cells. In line with the overall protective effect, blood levels of major SCFAs, such as acetate, propionate and butyrate, are significantly decreased in long-term active progressive multiple sclerosis (MS) patients. Importantly, SCFAs can induce CD4+ effector T cells, which are highly inflammatory when transferred into mice, suggesting that the direct effect of SCFAs on T cells can even be pro-inflammatory in the CNS. In contrast to the moderate protective effect of SCFAs, mice deficient in GPR41 or GPR43 are more resistant to EAE pathogenesis. Thus, despite the overall protective function of SCFAs, SCFAs and their receptors have the potential to regulate autoimmune CNS inflammation both positively and negatively.
https://www.eboro.cz
Re: SCFAs
Free full text. https://www.ncbi.nlm.nih.gov/pmc/articl ... _45311.pdfPetr75 wrote: ↑Wed Aug 21, 2019 11:18 am 2019 Jun 20
Department of Comparative Pathobiology, Purdue University, West Lafayette
Bidirectional regulatory potentials of short-chain fatty acids and their G-protein-coupled receptors in autoimmune neuroinflammation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586800/