Unexpected regulatory role of CCR9 in regulatory T cell development

Heather L. Evans-Marin, Anthony T. Cao, Suxia Yao, Feidi Chen, Chong He, Han Liu, Wei Wu, Maria G. Gonzalez, Sara Dann-Grice, Yingzi Cong

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15 Scopus citations

Abstract

T cells reactive to microbiota regulate the pathogenesis of inflammatory bowel disease (IBD). As T cell trafficking to intestines is regulated through interactions between highly specific chemokine-chemokine receptors, efforts have been made to develop intestine-specific immunosuppression based on blocking these key processes. CCR9, a gut-trophic chemokine receptor expressed by lymphocytes and dendritic cells, has been implicated in the regulation of IBD through mediating recruitment of T cells to inflamed sites. However, the role of CCR9 in inducing and sustaining inflammation in the context of IBD is poorly understood. In this study, we demonstrate that CCR9 deficiency in effector T cells and Tregs does not affect the development of colitis in a microbiota antigen-specific, T cell-mediated model. However, Treg cells express higher levels of CCR9 compared to those in effector T cells. Interestingly, CCR9 inhibits Treg cell development, in that CCR9<sup>-/-</sup> mice demonstrate a high level of Foxp3<sup>+</sup> Tregs, and ligation of CCR9 by its ligand CCL25 inhibits Treg cell differentiation in vitro. Collectively, our data indicate that in addition to acting as a gut-homing molecule, CCR9 signaling shapes immune responses by inhibiting Treg cell development.

Original languageEnglish (US)
Article numbere0134100
JournalPLoS One
Volume10
Issue number7
DOIs
StatePublished - Jul 31 2015

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Evans-Marin, H. L., Cao, A. T., Yao, S., Chen, F., He, C., Liu, H., Wu, W., Gonzalez, M. G., Dann-Grice, S., & Cong, Y. (2015). Unexpected regulatory role of CCR9 in regulatory T cell development. PLoS One, 10(7), [e0134100]. https://doi.org/10.1371/journal.pone.0134100