2011
DOI: 10.4049/jimmunol.1003251
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IL-17+ Regulatory T Cells in the Microenvironments of Chronic Inflammation and Cancer

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… Show more

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Cited by 233 publications
(223 citation statements)
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“…In humans, IL-17-producing Foxp3 þ T cells were identified in peripheral blood as well as in the microenvironments of chronic inflammation and cancer. 23,[45][46][47] Although most of these studies indicated that human Foxp3 þ IL-17 þ cells retain regulatory capacity as long as they express Foxp3, it was suggested that they can foster the expression of proinflammatory cytokines and thus behave as ''inflammatory'' Tregs. 23 In addition, in vitro studies showed that human RORgt þ Th17 cells preferentially differentiate from naïve Foxp3 þ T cells that lose their Foxp3 expression 48 that may eventually lead to conversion into pathogenic Th17 cells under inflammatory conditions.…”
Section: Discussionmentioning
confidence: 99%
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“…In humans, IL-17-producing Foxp3 þ T cells were identified in peripheral blood as well as in the microenvironments of chronic inflammation and cancer. 23,[45][46][47] Although most of these studies indicated that human Foxp3 þ IL-17 þ cells retain regulatory capacity as long as they express Foxp3, it was suggested that they can foster the expression of proinflammatory cytokines and thus behave as ''inflammatory'' Tregs. 23 In addition, in vitro studies showed that human RORgt þ Th17 cells preferentially differentiate from naïve Foxp3 þ T cells that lose their Foxp3 expression 48 that may eventually lead to conversion into pathogenic Th17 cells under inflammatory conditions.…”
Section: Discussionmentioning
confidence: 99%
“…23,[45][46][47] Although most of these studies indicated that human Foxp3 þ IL-17 þ cells retain regulatory capacity as long as they express Foxp3, it was suggested that they can foster the expression of proinflammatory cytokines and thus behave as ''inflammatory'' Tregs. 23 In addition, in vitro studies showed that human RORgt þ Th17 cells preferentially differentiate from naïve Foxp3 þ T cells that lose their Foxp3 expression 48 that may eventually lead to conversion into pathogenic Th17 cells under inflammatory conditions. 49 Additional studies in mice have shown that Foxp3 þ RORgt þ T cells have a regulatory function during autoimmune diabetes; 50 nevertheless, it was proposed that these cells represent intermediates that can differentiate either toward Foxp3 þ RORgt À Tregs or RORgt þ Foxp3 À Th17 cells.…”
Section: Discussionmentioning
confidence: 99%
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“…First, intratumoral Tregs have been shown to display a consistent degree of functional heterogeneity, which may obviously influence prognosis and/or response to therapy. For instance, a subpopulation of Tregs expressing IL-17 has recently been detected within colorectal cancer lesions, and these cells have been shown to potently suppress T-cell activation while promoting the production of pro-inflammatory cytokines [105]. Second, distinct subsets of Tregs appear to specifically control limited subsets of Teffs.…”
Section: Clinical Significance Of Intratumoral Tregsmentioning
confidence: 99%
“…The cytokine-producing Treg in these studies were anergic in vitro without the addition of IL-2, and were suppressive in Tconv co-cultures ( Refs 54,68,70,71,72 A beneficial role in the protection against infection has been proposed for cytokineproducing Treg (Refs 54, 73, 76), with some evidence for specific expansion and cytokine production against certain pathogenic antigens (Refs 54, 76). Moreover, there is evidence that such Treg may play a beneficial role during transplantation (Refs 76, 78): if IFN-γ production is blocked or specifically knocked out in Treg in a transplant model, mice suffer from graftversus-host disease.…”
Section: Introductionmentioning
confidence: 98%