Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis

Nature Communications

Volumn 9, Issue 1, 2018, Pages

  Sun, Mingming ^a,b   Wu, Wei ^a,b   Chen, Liang ^a,b   Yang, Wenjing ^a,b   Huang, Xiangsheng ^b   Ma, Caiyun ^a   Chen, Feidi ^b   Xiao, Yi ^b   Zhao, Ye ^b   Ma, Chunyan ^b   Yao, Suxia ^b   Carpio, Victor H ^b   Dann, Sara M ^b   Zhao, Qihong ^c   Liu, Zhanju ^a   Cong, Yingzi ^b  

^a TONGJI UNIVERSITY   (China)

^b University of Texas Medical Branch School of Medicine   (United States)

^c BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; B LYMPHOCYTE INDUCED MATURATION PROTEIN 1; BUTYRIC ACID; CBIR1 ANTIGEN; FLAGELLIN; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 43; HISTONE DEACETYLASE; INTERLEUKIN 10; INTERLEUKIN 17; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PROPIONIC ACID; SHORT CHAIN FATTY ACID; STAT3 PROTEIN; UNCLASSIFIED DRUG; CBIR1 FLAGELLIN; FFAR2 PROTEIN, MOUSE; IL10 PROTEIN, MOUSE; MTOR PROTEIN, MOUSE; PRDM1 PROTEIN, MOUSE; STAT3 PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; VOLATILE FATTY ACID;

ANTIGEN; BIOLOGICAL PRODUCTION; CELL; FATTY ACID; HOMEOSTASIS; MATURATION; MICROORGANISM; PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL DIFFERENTIATION; CONTROLLED STUDY; CYTOKINE PRODUCTION; DEXTRAN SULFATE SODIUM-INDUCED COLITIS; DRUG METABOLISM; ENZYME INHIBITION; HUMAN; IN VIVO STUDY; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; LYMPHOCYTE FUNCTION; MOUSE; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; T LYMPHOCYTE ACTIVATION; TH1 CELL; UPREGULATION; ANIMAL; COLITIS; GENE EXPRESSION; GENE KNOCKOUT; GENETICS; HOMEOSTASIS; IMMUNOLOGY; METABOLISM;

MUS;

ANIMALS; COLITIS; FATTY ACIDS, VOLATILE; FLAGELLIN; GASTROINTESTINAL MICROBIOME; GENE EXPRESSION; GENE KNOCKOUT TECHNIQUES; HOMEOSTASIS; INTERLEUKIN-10; MICE; POSITIVE REGULATORY DOMAIN I-BINDING FACTOR 1; RECEPTORS, G-PROTEIN-COUPLED; STAT3 TRANSCRIPTION FACTOR; TH1 CELLS; TOR SERINE-THREONINE KINASES; UP-REGULATION;

EID: 85052632504     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-018-05901-2     Document Type: Article

References (50)

1. Maloy, K. J. & Powrie, F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298–306 (2011).
2. Haghikia, A. et al. Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine. Immunity 44, 951–953 (2016).
3. Macia, L. et al. Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases. Immunol. Rev. 245, 164–176 (2012).
4. Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P. & Macfarlane, G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221–1227 (1987).
5. Sun, M., Wu, W., Liu, Z. & Cong, Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol. 52, 1–8 (2017).
6. Chang, P. V., Hao, L., Offermanns, S. & Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA 111, 2247–2252 (2014).
7. Ganapathy, V., Thangaraju, M., Prasad, P. D., Martin, P. M. & Singh, N. Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr. Opin. Pharmacol. 13, 869–874 (2013).
8. Kim, C. H., Park, J. & Kim, M. Gut microbiota-derived short-chain fatty acids, T cells, and inflammation. Immune Netw. 14, 277–288 (2014).
9. Brown, A. J. et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278, 11312–11319 (2003).
10. Macia, L. et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 6, 6734 (2015).
11. Lukasova, M., Malaval, C., Gille, A., Kero, J. & Offermanns, S. Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J. Clin. Invest. 121, 1163–1173 (2011).
12. Zhao, Y. et al. GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol. 11, 752–762 (2018).
13. Wu, W. et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. Mucosal Immunol. 10, 946–956 (2017).
14. Park, J. et al. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 8, 80–93 (2015).
15. Feng, T. et al. Th17 cells induce colitis and promote Th1 cell responses through IL-17 induction of innate IL-12 and IL-23 production. J. Immunol. 186, 6313–6318 (2011).
16. Globig, A. M. et al. Comprehensive intestinal T helper cell profiling reveals specific accumulation of IFN-gamma+IL-17+coproducing CD4+T cells in active inflammatory bowel disease. Inflamm. Bowel Dis. 20, 2321–2329 (2014).
17. Wu, W., Chen, F., Liu, Z. & Cong, Y. Microbiota-specific Th17 Cells: Yin and Yang in regulation of inflammatory bowel disease. Inflamm. Bowel Dis. 22, 1473–1482 (2016).
18. Huber, S. et al. Th17 cells express interleukin-10 receptor and are controlled by Foxp3(-) and Foxp3+regulatory CD4+T cells in an interleukin-10-dependent manner. Immunity 34, 554–565 (2011).
19. Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K. & Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263–274 (1993).
20. Cao, Y. et al. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Sci. Transl. Med. 7, 287ra274 (2015).
21. Franke, A. et al. Replication of signals from recent studies of Crohn’s disease identifies previously unknown disease loci for ulcerative colitis. Nat. Genet. 40, 713–715 (2008).
22. Begue, B. et al. Defective IL10 signaling defining a subgroup of patients with inflammatory bowel disease. Am. J. Gastroenterol. 106, 1544–1555 (2011).
23. Glocker, E. O. et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N. Engl. J. Med. 361, 2033–2045 (2009).
24. Roers, A. et al. T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J. Exp. Med. 200, 1289–1297 (2004).
25. Maslowski, K. M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282–1286 (2009).
26. Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).
27. Cong, Y., Feng, T., Fujihashi, K., Schoeb, T. R. & Elson, C. O. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc. Natl Acad. Sci. USA 106, 19256–19261 (2009).
28. Cretney, E. et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells. Nat. Immunol. 12, 304–311 (2011).
29. Montes de Oca, M. et al. Blimp-1-dependent IL-10 production by Tr1 cells regulates TNF-mediated tissue pathology. PLoS Pathog. 12, e1005398 (2016).
30. Neumann, C. et al. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J. Exp. Med. 211, 1807–1819 (2014).
31. Gateva, V. et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat. Genet. 41, 1228–1233 (2009).
32. Raychaudhuri, S. et al. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat. Genet. 41, 1313–1318 (2009).
33. Anderson, C. A. et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat. Genet. 43, 246–252 (2011).
34. Ellinghaus, D. et al. Association between variants of PRDM1 and NDP52 and Crohn’s disease, based on exome sequencing and functional studies. Gastroenterology 145, 339–347 (2013).
35. Kwon, H. et al. Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors. Immunity 31, 941–952 (2009).
36. Fung, M. M., Rohwer, F. & McGuire, K. L. IL-2 activation of a PI3K-dependent STAT3 serine phosphorylation pathway in primary human T cells. Cell. Signal. 15, 625–636 (2003).
37. Poholek, A. C. et al. IL-10 induces a STAT3-dependent autoregulatory loop in TH2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes. Sci. Immunol. 1, eaaf8612 (2016).
38. Zeng, H. & Chi, H. mTOR signaling in the differentiation and function of regulatory and effector T cells. Curr. Opin. Immunol. 46, 103–111 (2017).
39. Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
40. Liu, H. P. et al. TGF-beta converts Th1 cells into Th17 cells through stimulation of Runx1 expression. Eur. J. Immunol. 45, 1010–1018 (2015).
41. Feng, T., Cao, A. T., Weaver, C. T., Elson, C. O. & Cong, Y. Interleukin-12 converts Foxp3(+) regulatory T cells to interferon-gamma-producing Foxp3(+) T cells that inhibit colitis. Gastroenterology 140, 2031–2043 (2011).
42. Scheppach, W. et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology 103, 51–56 (1992).
43. Hamer, H. M. et al. Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission. Clin. Nutr. 29, 738–744 (2010).
44. Shapiro-Shelef, M. et al. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity 19, 607–620 (2003).
45. Kallies, A. et al. Initiation of plasma-cell differentiation is independent of the transcription factor Blimp-1. Immunity 26, 555–566 (2007).
46. Kallies, A. et al. Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance. Nat. Immunol. 7, 466–474 (2006).
47. Martins, G. A. et al. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat. Immunol. 7, 457–465 (2006).
48. Lin, M. H. et al. B lymphocyte-induced maturation protein 1 (BLIMP-1) attenuates autoimmune diabetes in NOD mice by suppressing Th1 and Th17 cells. Diabetologia 56, 136–146 (2013).
49. Heinemann, C. et al. IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+T cells by inducing Blimp1. Nat. Commun. 5, 3770 (2014).
50. Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783–784 (2014).