Commensal bacteria regulate thymic Aire expression

PLoS One. 2014 Aug 26;9(8):e105904. doi: 10.1371/journal.pone.0105904. eCollection 2014.

Abstract

Commensal bacteria in gastrointestinal tracts are reported to function as an environmental factor to regulate intestinal inflammation and immune responses. However, it remains largely unknown whether such bacterial function exerts any effect on other immune organs distant from the intestine. In this study, the influence of commensal bacteria in the thymus, where T cell lineages develop into mature type to form proper repertoires, was investigated using germ-free (GF) mice and Nod1-deficient mice lacking an intracellular recognition receptor for certain bacterial components, in which a commensal bacterial effect is predicted to be less. In both mice, there was no significant difference in the numbers and subset ratios of thymocytes. Interestingly, however, autoimmune regulator (Aire) expression in thymic epithelial cells (TECs), main components of the thymic microenvironment, was decreased in comparison to specific pathogen-free (SPF) mice and Nod1 wild-type (WT) mice, respectively. In vitro analysis using a fetal thymus organ culture (FTOC) system showed that Aire expression in TECs was increased in the presence of a bacterial component or a bacterial product. These results suggest that through their products, commensal bacteria have the potential to have some effect on epithelial cells of the thymus in tissues distant from the intestine where they are originally harbored.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIRE Protein
  • Animals
  • Gastrointestinal Tract / microbiology
  • Gene Expression
  • Germ-Free Life
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microbiota / physiology*
  • Thymocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism*
  • Tissue Culture Techniques
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • Transcription Factors

Grants and funding

This work was supported in part a Grant-in-Aid for Scientific Research (B) (SH; 21390154), a Grant-in-Aid for Scientific Research (B) (KO; 23390260), and a Grant-in-Aid for Scientific Research Young Scientist (B) (AN; 25860818) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (http://www.jsps.go.jp/english/e-grants/), and the Yakult -Bio-Science foundation (http://yakult-bioscience.or.jp/index.html) for AN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.