Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma

Ilona Kryczek, Lin Wang, Ke Wu, Wei Li, Ende Zhao, Tracy Cui, Shuang Wei, Yan Liu, Yin Wang, Linda Vatan, Wojciech Szeliga, Joel K. Greenson, Jacek Roliński, Witold Zgodzinski, Emina Huang, Kaixiong Tao, Guobin Wang, Weiping Zou

Research output: Contribution to journalArticlepeer-review

Abstract

Foxp3+CD4+ regulatory T (Treg) cells are thought to express negligible levels of effector cytokines, and inhibit immune responses and inflammation. Here, we have identified a population of IL-8+Foxp3+CD4+ T cells in human peripheral blood, which is selectively increased in the microenvironments of ulcerative colitis and colon carcinoma. Phenotypically, this population is minimally overlapping with IL-17+Foxp3+CD4+ T cells, and is different from IL-8Foxp3+CD4+ T cells in the same microenvironment. 40–60% of IL-8+Foxp3+CD4+ T cells exhibit naive phenotype and express CD127, whereas IL-8Foxp3+CD4+ cells are basically memory T cells and express minimal CD127. The levels of CXCR5 expression are higher in IL-8+Foxp3+ cells than in IL-8Foxp3+ cells. IL-2 and TGFβ induce IL-8+Foxp3+ T cells. Exogenous Foxp3 expression promotes IL-8+Foxp3+ T cells and inhibits effector cytokine IFNγ and IL-2 expression. Furthermore, Foxp3 binds to IL-8 proximal promoter and increases its activity. Functionally, IL-8+Foxp3+ T cells inhibit T cell proliferation and effector cytokine production, but stimulate inflammatory cytokine production in the colon tissues, and promote neutrophil trafficking through IL-8. Thus, IL-8+Foxp3+ cells may be an “inflammatory” Treg subset, and possess inflammatory and immunosuppressive dual biological activities. Given their dual roles and localization, these cells may be in a unique position to support tumor initiation and development in human chronic inflammatory environment.

Original languageEnglish (US)
Article numbere1105430
JournalOncoImmunology
Volume5
Issue number8
DOIs
StatePublished - Aug 2 2016
Externally publishedYes

Keywords

  • Colon carcinoma
  • IL-17
  • IL-8
  • Regulatory T cell
  • Th17
  • neutrophil
  • tumor immunity
  • ulcerative colitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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