Requirement of full TCR repertoire for regulatory T cells to maintain intestinal homeostasis

Junko Nishio, Minato Baba, Koji Atarashi, Takeshi Tanoue, Hideo Negishi, Hideyuki Yanai, Sonoko Habu, Shohei Hori, Kenya Honda, Tadatsugu Taniguchi

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)


The regulation of intestinal homeostasis by the immune system involves the dynamic interplay between gut commensal microbiota and resident immune cells. It is well known that a large and diverse lymphocyte antigen receptor repertoire enables the immune system to recognize and respond to a wide range of invading pathogens. There is also an emerging appreciation for a critical role the T-cell receptor (TCR) repertoire serves in the maintenance of peripheral tolerance by regulatory T cells (Tregs). Nevertheless, how the diversity of the TCR repertoire in Tregs affects intestinal homeostasis remains unknown. To address this question, we studied mice whose T cells express a restricted TCR repertoire. We observed the development of spontaneous colitis, accompanied by the induction of T-helper type 17 cells in the colon that is driven by gut commensal microbiota. We provide further evidence that a restricted TCR repertoire causes a loss of tolerogenicity to microbiota, accompanied by a paucity of peripherally derived, Helios- Tregs and hyperactivation of migratory dendritic cells. These results thus reveal a new facet of the TCR repertoire in which Tregs require a diverse TCR repitoire for intestinal homeostasis, suggesting an additional driving force in the evolutional significance of the TCR repertoire.

Original languageEnglish
Pages (from-to)12770-12775
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number41
Publication statusPublished - 2015 Oct 13


  • Colitis
  • Helios
  • Migratory DCs
  • TCR repertoire
  • Treg

ASJC Scopus subject areas

  • General


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