IL-17+ regulatory T Cells in the microenvironments of chronic inflammation and cancer

Ilona Kryczek, Ke Wu, Ende Zhao, Shuang Wei, Linhua Vatan, Wojciech Szeliga, Emina Huang, Joel Greenson, Alfred Chang, Jacek Roliński, Piotr Radwan, Jingyuan Fang, Guobin Wang, Weiping Zou

Research output: Contribution to journalArticlepeer-review

Abstract

Foxp3+CD4+ regulatory T (Treg) cells inhibit immune responses and temper inflammation. IL-17+CD4+ T (Th17) cells mediate inflammation of autoimmune diseases. A small population of IL-17+Foxp3+CD4+ T cells has been observed in peripheral blood in healthy human beings. However, the biology of IL-17 +Foxp3+CD4+ T cells remains poorly understood in humans. We investigated their phenotype, cytokine profile, generation, and pathological relevance in patients with ulcerative colitis. We observed that high levels of IL-17+Foxp3+CD4+ T cells were selectively accumulated in the colitic microenvironment and associated colon carcinoma. The phenotype and cytokine profile of IL-17+Foxp3 +CD4+ T cells was overlapping with Th17 and Treg cells. Myeloid APCs, IL-2, and TGF-b are essential for their induction from memory CCR6+ T cells or Treg cells. IL-17+Foxp3 +CD4+ T cells functionally suppressed T cell activation and stimulated inflammatory cytokine production in the colitic tissues. Our data indicate that IL-17+ Foxp3+ cells may be "inflammatory" Treg cells in the pathological microenvironments. These cells may contribute to the pathogenesis of ulcerative colitis through inducing inflammatory cytokines and inhibiting local T cell immunity, and in turn may mechanistically link human chronic inflammation to tumor development. Our data therefore challenge commonly held beliefs of the anti-inflammatory role of Treg cells and suggest a more complex Treg cell biology, at least in the context of human chronic inflammation and associated carcinoma. The Journal of Immunology, 2011, 186: 4388-4395.

Original languageEnglish (US)
Pages (from-to)4388-4395
Number of pages8
JournalJournal of Immunology
Volume186
Issue number7
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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