Inflammatory regulatory T cells in the microenvironments of ulcerative colitis and colon carcinoma. (2nd August 2016)

• Record Type: Journal Article
• Authors: Kryczek, Ilona; Wang, Lin; Wu, Ke; Li, Wei; Zhao, Ende; Cui, Tracy; Wei, Shuang; Liu, Yan; Wang, Yin; Vatan, Linda; Szeliga, Wojciech; Greenson, Joel K.; Roliński, Jacek; Zgodzinski, Witold; Huang, Emina; Tao, Kaixiong; Wang, Guobin; Zou, Weiping
• Is Part Of: Oncoimmunology. Volume 5:Number 8(2016)
• Publication Date: 2016-08-02
• Subjects: Colon carcinoma -- IL-8 -- IL-17 -- neutrophil -- Regulatory T cell -- Th17 -- tumor immunity -- ulcerative colitis; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2015.1105430
• Languages: English
• ISSNs: 2162-402X

Abstract

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-8 − Foxp3 + CD4 + T cells in the same microenvironment. 40–60% of IL-8 + Foxp3 + CD4 + T cells exhibit naive phenotype and express CD127, whereas IL-8 − Foxp3 + 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-8 − Foxp3 + 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.