Identification of a Chemokine Network That Recruits FoxP3+ Regulatory T Cells Into Chronically Inflamed Intestine

Seung G. Kang, Ronald J. Piniecki, Harm Hogenesch, Hyung W. Lim, Eric Wiebke, Stephen E. Braun, Satoshi Matsumoto, Chang H. Kim

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background & Aims: It has been unclear which chemokine network is involved in migration of T-cell subsets to chronically inflamed lesions of the intestine. SAMP1/YP mice develop a spontaneous chronic transmural intestinal lesion specifically in the ileum. Using these mice, we investigated the gut chemokine network involved in specific migration of T-cell subsets to the inflamed lesion of the intestine. Methods: We performed expression analyses of chemokines and their receptors, chemokine receptor blocking studies, and migration studies in vitro and in vivo to identify the gut chemokine network induced in intestinal inflammation and to determine its role in migration of conventional and FoxP3+ suppressor T cells to the inflamed intestine. Results: The expression of homeostatic chemokines was largely unchanged in the inflamed lesion of SAMP1/YP mice compared with control mice. However, an additional chemokine axis (CCL5-CCR5) was up-regulated in the inflamed intestine of SAMP1/YP mice compared with control mice. Activated T cells of SAMP1/YP mice compared with control mice were hyperresponsive to CCL5 in chemotaxis. CCR5+ T cells preferentially migrated to the inflamed lesion, which can be blocked by a CCR5 antagonist. Importantly, the FoxP3+ regulatory T cells of the inflamed lesion of SAMP1/YP mice highly expressed CCR5. CCR5 blockade suppressed the migration of FoxP3+ T cells into the inflamed intestine and significantly exacerbated the intestinal inflammation. Conclusions: The CCL5-CCR5 chemokine axis is involved in preferential recruitment of FoxP3+ regulatory T cells, which prevents further exacerbation of chronic inflammation in the intestine.

Original languageEnglish (US)
Pages (from-to)966-981
Number of pages16
JournalGastroenterology
Volume132
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Fingerprint Dive into the research topics of 'Identification of a Chemokine Network That Recruits FoxP3<sup>+</sup> Regulatory T Cells Into Chronically Inflamed Intestine'. Together they form a unique fingerprint.

  • Cite this