Deficiency of Stearoyl-CoA Desaturase-1 Aggravates Colitogenic Potential of Adoptively Transferred Effector T Cells

Overview

Journal Am J Physiol Gastrointest Liver Physiol

Publisher American Physiological Society

Specialties Gastroenterology
Physiology

Date 2016 Sep 10

PMID 27609767

Citations 5

Authors

Beng San Yeoh

Piu Saha

Vishal Singh

Xia Xiao

Yun Ying

Jairam K Vanamala

Mary J Kennett

Kevin J Harvatine

Bina Joe

Matam Vijay-Kumar

Affiliations

Soon will be listed here.

Abstract

Stearoyl-CoA desaturase-1 (SCD1) is a lipogenic enzyme involved in the de novo biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of lipid bilayers of cell membranes. Accordingly, Scd1KO mice display substantially reduced oleate in cell membranes. An altered SCD1 level was observed during intestinal inflammation; however, its role in modulating inflammatory bowel disease remains elusive. Herein, we investigated the colitogenic capacity of Scd1KO effector T cells by employing the adoptive T-cell transfer colitis model. Splenic effector T cells (CD4CD25) from age- and sex-matched wild-type (WT) and Scd1KO mice were isolated by FACS and intraperitoneally administered to Rag1KO mice, which were monitored for the development of colitis. At day 60 postcell transfer, Rag1KO mice that received Scd1KO CD4CD25 T cells displayed accelerated and exacerbated colitis than mice receiving WT CD4CD25 T cells. Intriguingly, Scd1KO CD4CD25 T cells display augmented inflammatory cytokine profile and cellular membrane fluidity with a concomitant increase in proinflammatory saturated fatty acids, which we postulate to potentially underlie their augmented colitogenic potential.

Citing Articles

Stearoyl-CoA desaturase-1: a potential therapeutic target for neurological disorders.

Loix M, Vanherle S, Turri M, Kemp S, Fernandes K, Hendriks J Mol Neurodegener. 2024; 19(1):85.

PMID: 39563397 PMC: 11575020. DOI: 10.1186/s13024-024-00778-w.

Stearoyl-CoA desaturase in CD4 T cells suppresses tumor growth through activation of the CXCR3/CXCL11 axis in CD8 T cells.

Hwang S, Yang Y, Jung J, Kim J, Kim Y Cell Biosci. 2024; 14(1):137.

PMID: 39543650 PMC: 11566202. DOI: 10.1186/s13578-024-01308-3.

Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity.

Grajchen E, Loix M, Baeten P, Corte-Real B, Hamad I, Vanherle S Cell Mol Immunol. 2023; 20(6):666-679.

PMID: 37041314 PMC: 10229556. DOI: 10.1038/s41423-023-01011-2.

Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.

Gokula V, Terrero D, Joe B Curr Hypertens Rep. 2022; 24(12):669-685.

PMID: 36301488 PMC: 9708772. DOI: 10.1007/s11906-022-01226-0.

Increased intestinal permeability exacerbates sepsis through reduced hepatic SCD-1 activity and dysregulated iron recycling.

Kumar M, Leon Coria A, Cornick S, Petri B, Mayengbam S, Jijon H Nat Commun. 2020; 11(1):483.

PMID: 31980623 PMC: 6981269. DOI: 10.1038/s41467-019-14182-2.

References

Liu X, Strable M, Ntambi J . Stearoyl CoA desaturase 1: role in cellular inflammation and stress. Adv Nutr. 2012; 2(1):15-22. PMC: 3042787. DOI: 10.3945/an.110.000125. View

Lone A, Tasken K . Proinflammatory and immunoregulatory roles of eicosanoids in T cells. Front Immunol. 2013; 4:130. PMC: 3671288. DOI: 10.3389/fimmu.2013.00130. View

Berod L, Friedrich C, Nandan A, Freitag J, Hagemann S, Harmrolfs K . De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells. Nat Med. 2014; 20(11):1327-33. DOI: 10.1038/nm.3704. View

Koberlin M, Snijder B, Heinz L, Baumann C, Fauster A, Vladimer G . A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses. Cell. 2015; 162(1):170-83. PMC: 4523684. DOI: 10.1016/j.cell.2015.05.051. View

Vijay-Kumar M, Sanders C, Taylor R, Kumar A, Aitken J, Sitaraman S . Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest. 2007; 117(12):3909-21. PMC: 2075480. DOI: 10.1172/JCI33084. View

Miyazaki M, Dobrzyn A, Sampath H, Lee S, Man W, Chu K . Reduced adiposity and liver steatosis by stearoyl-CoA desaturase deficiency are independent of peroxisome proliferator-activated receptor-alpha. J Biol Chem. 2004; 279(33):35017-24. DOI: 10.1074/jbc.M405327200. View

Scaglia N, Igal R . Inhibition of Stearoyl-CoA Desaturase 1 expression in human lung adenocarcinoma cells impairs tumorigenesis. Int J Oncol. 2008; 33(4):839-50. View

Ntambi J, Miyazaki M, Stoehr J, Lan H, Kendziorski C, Yandell B . Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci U S A. 2002; 99(17):11482-6. PMC: 123282. DOI: 10.1073/pnas.132384699. View

Szamel M, Rehermann B, Krebs B, Kurrle R, Resch K . Activation signals in human lymphocytes. Incorporation of polyunsaturated fatty acids into plasma membrane phospholipids regulates IL-2 synthesis via sustained activation of protein kinase C. J Immunol. 1989; 143(9):2806-13. View

10.

Stentz F, Kitabchi A . Palmitic acid-induced activation of human T-lymphocytes and aortic endothelial cells with production of insulin receptors, reactive oxygen species, cytokines, and lipid peroxidation. Biochem Biophys Res Commun. 2006; 346(3):721-6. DOI: 10.1016/j.bbrc.2006.05.159. View

11.

Flowers M, Keller M, Choi Y, Lan H, Kendziorski C, Ntambi J . Liver gene expression analysis reveals endoplasmic reticulum stress and metabolic dysfunction in SCD1-deficient mice fed a very low-fat diet. Physiol Genomics. 2008; 33(3):361-72. DOI: 10.1152/physiolgenomics.00139.2007. View

12.

Ntambi J, Buhrow S, Kaestner K, Christy R, Sibley E, Kelly Jr T . Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. J Biol Chem. 1988; 263(33):17291-300. View

13.

Cury-Boaventura M, Kanunfre C, Gorjao R, de Lima T, Curi R . Mechanisms involved in Jurkat cell death induced by oleic and linoleic acids. Clin Nutr. 2006; 25(6):1004-14. DOI: 10.1016/j.clnu.2006.05.008. View

14.

Krugner-Higby L, Brown R, Rassette M, Behr M, Okwumabua O, Cook M . Ulcerative dermatitis in C57BL/6 mice lacking stearoyl CoA desaturase 1. Comp Med. 2012; 62(4):257-63. PMC: 3415366. View

15.

Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C . Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes. 2002; 51(5):1437-42. DOI: 10.2337/diabetes.51.5.1437. View

16.

Macdonald M, Van Eck M, Hildebrand R, Wong B, Bissada N, Ruddle P . Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol. 2008; 29(3):341-7. PMC: 2873333. DOI: 10.1161/ATVBAHA.108.181099. View

17.

Hellemans K, Hannaert J, Denys B, Steffensen K, Raemdonck C, Martens G . Susceptibility of pancreatic beta cells to fatty acids is regulated by LXR/PPARalpha-dependent stearoyl-coenzyme A desaturase. PLoS One. 2009; 4(9):e7266. PMC: 2746288. DOI: 10.1371/journal.pone.0007266. View

18.

Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K . Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med. 2009; 15(6):633-40. DOI: 10.1038/nm.1968. View

19.

Hara A, RADIN N . Lipid extraction of tissues with a low-toxicity solvent. Anal Biochem. 1978; 90(1):420-6. DOI: 10.1016/0003-2697(78)90046-5. View

20.

Cohen P, Miyazaki M, Socci N, Hagge-Greenberg A, Liedtke W, Soukas A . Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science. 2002; 297(5579):240-3. DOI: 10.1126/science.1071527. View