IL-17 Amplifies Human Contact Hypersensitivity by Licensing Hapten Nonspecific Th1 Cells to Kill Autologous Keratinocytes

被引:100
作者
Pennino, Davide [1 ]
Eyerich, Kilian [1 ]
Scarponi, Claudia [1 ]
Carbone, Teresa [1 ]
Eyerich, Stefanie [3 ]
Nasorri, Francesca [1 ]
Garcovich, Simone [2 ]
Traidl-Hoffmann, Claudia [3 ]
Albanesi, Cristina [1 ]
Cavani, Andrea [1 ]
机构
[1] Ist Ricovero & Cura Carattere Sci, Expt Immunol Lab, Ist Dermopat Immacolata, I-00167 Rome, Italy
[2] Univ Cattolica Sacro Cuore, Policlin Gemelli, Dept Dermatol, Rome, Italy
[3] Tech Univ Munich, Div Environm Dermatol & Allergy, Zentrum Allergie & Umwelt, Munich, Germany
关键词
REGULATORY T-CELLS; ECZEMATOUS DERMATITIS; SKIN INFLAMMATION; IMMUNE-RESPONSES; INNATE; CD8(+); LYMPHOCYTES; PSORIASIS; NICKEL; ACTIVATION;
D O I
10.4049/jimmunol.0901767
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th17 is a newly identified lineage of effector T cells involved in autoimmunity and immune responses to pathogens. We demonstrate in this study the pathogenic role of IL-17-producing CD4(+) T lymphocytes in allergic contact dermatitis (ACD) to skin-applied chemicals. IL-17(+) T cells infiltrate ACD reactions and predominantly distribute at the site of heavy spongiosis. Skin IL-17(+) T cells were functionally and phenotypically heterogeneous: although pure Th17 prevailed in ACD skin, hapten responsiveness was restricted to Th1/IL-17 (IFN-gamma+IL-17(+)) and Th0/IL-17 (IFN-gamma+IL-17(+)IL-4(+)) fractions, and to lesser extent Th2/IL-17 cells. In the IFN-gamma-dominated ACD environment, IL-17-releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL-6, and HBD-2 production. In addition, compared with Th1, supernatants from Th1/IL-17 T cells were much more efficient in inducing ICAM-1 expression on keratinocytes and keratinocyte T cell adhesiveness in vitro. As a consequence, exposure to combined IFN-gamma and IL-17 rendered keratinocytes susceptible to ICAM-1 dependent Ag nonspecific T cell killing. Thus, IL-17 efficiently amplifies the allergic reaction by rendering virtually all of the T lymphocytes recruited at the site of skin inflammation capable to directly contribute to tissue damage. The Journal of Immunology, 2010, 184: 4880-4888.
引用
收藏
页码:4880 / 4888
页数:9
相关论文
共 36 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] Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-γ- and interleukin-4-induced activation of human keratinocytes
    Albanesi, C
    Scarponi, CS
    Cavani, A
    Federici, M
    Nasorri, F
    Girolomoni, G
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 115 (01) : 81 - 87
  • [3] Albanesi Cristina, 2005, Current Drug Targets - Inflammation and Allergy, V4, P329, DOI 10.2174/1568010054022033
  • [4] Phenotypic and functional features of human Th17 cells
    Annunziato, Francesco
    Cosmi, Lorenzo
    Santarlasci, Veronica
    Maggi, Laura
    Liotta, Francesco
    Mazzinghi, Benedetta
    Parente, Eliana
    Fili, Lucia
    Ferri, Simona
    Frosali, Francesca
    Giudici, Francesco
    Romagnani, Paola
    Parronchi, Paola
    Tonelli, Francesco
    Maggi, Enrico
    Romagnani, Sergio
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (08) : 1849 - 1861
  • [5] Human Th17 cells: Are they different from murine Th17 cells?
    Annunziato, Francesco
    Cosmi, Lorenzo
    Liotta, Francesco
    Maggi, Enrico
    Romagnani, Sergio
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2009, 39 (03) : 637 - 640
  • [6] Human CD4+ T lymphocytes with remarkable regulatory functions on dendritic cells and nickel-specific Th1 immune responses
    Cavani, A
    Nasorri, F
    Prezzi, C
    Sebastiani, S
    Albanesi, C
    Girolomoni, G
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 114 (02) : 295 - 302
  • [7] Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals
    Cavani, A
    Nasorri, F
    Ottaviani, C
    Sebastiani, S
    De Pità, O
    Girolomoni, G
    [J]. JOURNAL OF IMMUNOLOGY, 2003, 171 (11) : 5760 - 5768
  • [8] New aspects of the molecular basis of contact allergy
    Cavani, Andrea
    De Pita, Ornella
    Girolomoni, Giampiro
    [J]. CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2007, 7 (05) : 404 - 408
  • [9] 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
  • [10] Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation
    Dubois, B
    Chapat, L
    Goubier, A
    Papiernik, M
    Nicolas, JF
    Kaiserlian, D
    [J]. BLOOD, 2003, 102 (09) : 3295 - 3301