Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation

Nature

Volumn 504, Issue 7480, 2013, Pages 451-455

  Arpaia, Nicholas ^a   Campbell, Clarissa ^a   Fan, Xiying ^a   Dikiy, Stanislav ^a   Van Der Veeken, Joris ^a   Deroos, Paul ^a   Liu, Hui ^a   Cross, Justin R ^a   Pfeffer, Klaus ^b   Coffer, Paul J ^a,c   Rudensky, Alexander Y ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b HEINRICH HEINE UNIVERSITY   (Germany)

^c UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BUTYRIC ACID; HISTONE DEACETYLASE; PROPIONIC ACID; TRANSCRIPTION FACTOR FOXP3;

BACTERIUM; HOMEOSTASIS; HYPOTHESIS TESTING; IMMUNE SYSTEM; INHIBITOR; METABOLITE; MICROBIAL COMMUNITY;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CD4+ T LYMPHOCYTE; CELL COUNT; CELL DIFFERENTIATION; CELL LINE; CELL REGENERATION; COMMENSAL; CONTROLLED STUDY; DENDRITIC CELL; ENHANCER REGION; ENTERITIS; ENZYME INHIBITION; HISTONE ACETYLATION; IMMUNE SYSTEM; INTESTINE FLORA; MALE; METABOLITE; MICROBIAL METABOLITE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; TH17 CELL;

ACETYLATION; ANIMALS; BUTYRATES; CELL DIFFERENTIATION; CYTOKINES; DENDRITIC CELLS; ENHANCER ELEMENTS, GENETIC; FERMENTATION; FORKHEAD TRANSCRIPTION FACTORS; HISTONE DEACETYLASES; INFLAMMATION MEDIATORS; INTESTINAL MUCOSA; INTESTINES; INTRONS; LYMPHOCYTE COUNT; MALE; MICE; MICE, INBRED C57BL; STARCH; SYMBIOSIS; T-LYMPHOCYTES, REGULATORY;

BACTERIA (MICROORGANISMS); MUS;

EID: 84890550163     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature12726     Document Type: Article

References (25)

1. Josefowicz, S. Z. et al. Extrathymically generated regulatory T cells controlmucosal TH2 inflammation. Nature 482, 395-399 (2012).
2. Round, J. L. & Mazmanian, S. K. Inducible Foxp31 regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc. Natl Acad. Sci. USA 107, 12204-12209 (2010).
3. Ivanov, I. I. et al. Induction of intestinal TH17 cells by segmented filamentous bacteria. Cell 139, 485-498 (2009).
4. Lathrop, S. K. et al. Peripheral education of the immune system by colonic commensal microbiota. Nature 478, 250-254 (2011).
5. Atarashi, K. et al. Induction of colonic regulatory T cells by indigenous clostridium species. Science 331, 337-341 (2011).
6. Atarashi, K. et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 500, 232-236 (2013).
7. Zheng, Y. et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463, 808-812 (2010).
8. Annison, G. , Illman, R. J. & Topping, D. L. Acetylated, propionylated or butyrylated starches raise large bowel short-chain fatty acids preferentially when fed to rats. J. Nutr. 133, 3523-3528 (2003).
9. Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569-573 (2013).
10. van Loosdregt, J. et al. Rapid temporal control of Foxp3 protein degradation by sirtuin-1. PLoS ONE 6, e19047 (2011).
11. van Loosdregt, J. et al. Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Blood 115, 965-974 (2010).
12. Zhang, H. , Xiao, Y. , Zhu, Z. , Li, B. & Greene, M. I. Immune regulation by histone deacetylases: a focus on the alteration of FOXP3 activity. Immunol. Cell Biol. 90, 95-100 (2012).
13. Song, X. et al. Structural and biological features of FOXP3 dimerization relevant to regulatory T cell function. Cell Rep. 1, 665-675 (2012).
14. Wang, L. , de Zoeten, E. F. , Greene, M. I. & Hancock, W. W. Immunomodulatory effects of deacetylase inhibitors: therapeutic targeting of FOXP31 regulatory T cells. Nature Rev. Drug Discov. 8, 969-981 (2009).
15. Tao, R. et al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nature Med. 13, 1299-1307 (2007).
16. Maslowski, K. M. et al. Regulationof inflammatory responses bygut microbiota and chemoattractant receptor GPR43. Nature 461, 1282-1286 (2009).
17. Thangaraju, M. et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 69, 2826-2832 (2009).
18. Nilsson, N. E. , Kotarsky, K. , Owman, C. & Olde, B. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem. Biophys. Res. Commun. 303, 1047-1052 (2003).
19. MacDonald, K. P. et al. Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD. Blood 109, 5049-5057 (2007).
20. Zhu, H. C. et al. Tolerogenic dendritic cells generated by RelB silencing using shRNA prevent acute rejection. Cell. Immunol. 274, 12-18 (2012).
21. Shih, V. F. et al. Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-kB pathways. Nature Immunol. 13, 1162-1170 (2012).
22. Fontenot, J. D. et al. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity 22, 329-341 (2005).
23. Kim, J. M. , Rasmussen, J. P. & Rudensky, A. Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nature Immunol. 8, 191-197 (2007).
24. Torii, T. et al. Measurement of short-chain fatty acids in human faeces using highperformance liquid chromatography: specimen stability. Ann. Clin. Biochem. 47, 447-452 (2010).
25. Samstein, R. M. et al. Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. Cell 151, 153-166 (2012).