DC activated via dectin-1 convert Treg into IL-17 producers

被引:223
作者
Osorio, Fabiola [1 ]
LeibundGut-Landmann, Salome [1 ]
Lochner, Matthias [2 ]
Lahl, Katharina [3 ]
Sparwasser, Tim [3 ]
Eberl, Gerard [2 ]
Reis e Sousa, Caetano [1 ]
机构
[1] London Res Inst, Canc Res UK, Immunobiol Lab, Lincolns Inn Fields Labs, London, England
[2] Inst Pasteur, CNRS, Lab Lymphoid Tissue Dev, URA 1961, Paris, France
[3] Tech Univ Munich, Inst Med Mikrobiol Immunol & Hyg, Munich, Germany
关键词
DC; Dectin-1; Th17; Treg;
D O I
10.1002/eji.200838950
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th cells producing IL-17 play a pro-inflammatory role at mucosal surfaces. Treg at the same sites dampen inflammation and prevent immunopathology. Th cells producing IL-17 (Th17) and Treg are thought to be distinct populations defined by expression of the transcription factors ROR-gamma t and Foxp3, respectively. Here, we show that mouse CD25(+)Foxp3(+) Treg can be converted into a hybrid T-cell population characterized by the expression of Foxp3 and ROR-gamma t and the production of IL-17. Conversion was observed upon coculture with DC selectively activated via dectin-1, a C-type lectin receptor involved in fungal recognition, and depended on IL-23 produced by DC. Within the Foxp3(+) population, only Foxp3(+)ROR-gamma t(+) T cells but not Foxp3(+)ROR-gamma t(-)-T cells become Foxp3(+)IL-17(+) T cells. These results indicate that some Foxp3(+) T cells can produce IL-17 while retaining Foxp3 expression and suggest that Treg could play an unexpected pro-inflammatory role in some settings.
引用
收藏
页码:3274 / 3281
页数:8
相关论文
共 34 条
  • [1] Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells
    Acosta-Rodriguez, Eva V.
    Rivino, Laura
    Geginat, Jens
    Jarrossay, David
    Gattorno, Marco
    Lanzavecchia, Antonio
    Sallusto, Federica
    Napolitani, Giorgio
    [J]. NATURE IMMUNOLOGY, 2007, 8 (06) : 639 - 646
  • [2] Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells
    Bettelli, E
    Carrier, YJ
    Gao, WD
    Korn, T
    Strom, TB
    Oukka, M
    Weiner, HL
    Kuchroo, VK
    [J]. NATURE, 2006, 441 (7090) : 235 - 238
  • [3] Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance
    Dillon, S
    Agrawal, S
    Banerjee, K
    Letterio, J
    Denning, TL
    Oswald-Richter, K
    Kasprowicz, DJ
    Kellar, K
    Pare, J
    van Dyke, T
    Ziegler, S
    Unutmaz, D
    Pulendran, B
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (04) : 916 - 928
  • [4] TH 17 cells in development:: an updated view of their molecular identity and genetic programming
    Dong, Chen
    [J]. NATURE REVIEWS IMMUNOLOGY, 2008, 8 (05) : 337 - 348
  • [5] A function for interleukin 2 in Foxp3-expressing regulatory T cells
    Fontenot, JD
    Rasmussen, JP
    Gavin, MA
    Rudensky, AY
    [J]. NATURE IMMUNOLOGY, 2005, 6 (11) : 1142 - 1151
  • [6] Foxp3-dependent programme of regulatory T-cell differentiation
    Gavin, Marc A.
    Rasmussen, Jeffrey P.
    Fontenot, Jason D.
    Vasta, Valeria
    Manganiello, Vincent C.
    Beavo, Joseph A.
    Rudensky, Alexander Y.
    [J]. NATURE, 2007, 445 (7129) : 771 - 775
  • [7] Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice
    Ghilardi, N
    Kljavin, N
    Chen, Q
    Lucas, S
    Gurney, AL
    de Sauvage, FJ
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 172 (05) : 2827 - 2833
  • [8] Control of regulatory T cell development by the transcription factor Foxp3
    Hori, S
    Nomura, T
    Sakaguchi, S
    [J]. SCIENCE, 2003, 299 (5609) : 1057 - 1061
  • [9] Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice
    Huang, WT
    Na, L
    Fidel, PL
    Schwarzenberger, P
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2004, 190 (03) : 624 - 631
  • [10] The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells
    Ivanov, Ivaylo I.
    McKenzie, Brent S.
    Zhou, Liang
    Tadokoro, Carlos E.
    Lepelley, Alice
    Lafaille, Juan J.
    Cua, Daniel J.
    Littman, Dan R.
    [J]. CELL, 2006, 126 (06) : 1121 - 1133