Induction of IL-17+ T cell trafficking and development by IFN-γ:: Mechanism and pathological relevance in psoriasis

被引:373
作者
Kryczek, Ilona [1 ]
Bruce, Allen T. [2 ]
Gudjonsson, Johann E. [2 ]
Johnston, Andrew [2 ]
Aphale, Abhishek [2 ]
Vatan, Linhua [1 ]
Szeliga, Wojciech [1 ]
Wang, Yin [1 ]
Liu, Yan [1 ]
Welling, Theodore H. [1 ]
Elder, James T. [2 ,3 ,4 ,5 ]
Zou, Weiping [1 ]
机构
[1] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48105 USA
[2] Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI 48105 USA
[3] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48105 USA
[4] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA
[5] Ann Arbor Vet Affairs Hosp, Ann Arbor, MI 48105 USA
关键词
D O I
10.4049/jimmunol.181.7.4733
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th1 and Th17 T cells are often colocalized in pathological environments, yet Th1-derived IFN-gamma inhibits Th17 cell development in vitro. We explored the physiologic basis of this paradox in humans. In this study, we demonstrate increased the number of CD4(+) and CD8(+) IL-17(+) T cells in skin lesions of psoriasis. Furthermore, we show that myeloid APCs potently support induction of IL-1(+) T cells, and that this activity is greatly increased in psoriasis. We tested stimuli that might account for this activity. Th1 cells and IFN-gamma are increased in psoriatic blood and lesional skin. We show that IFN-gamma programs myeloid APCs to induce human IL-17(+) T cells via IL-1 and IL-23. IFN-gamma also stimulates APC production of CCL20, supporting migration of IL-17+ T cells, and synergizes with IL-17 in the production of human beta-defensin 2, an antimicrobial and chemotactic protein highly overexpressed by psoriatic keratinocytes. This study reveals a novel mechanistic interaction between Th1 and IL-17(+) T cells, challenges the view that Th1 cells suppress Th17 development through IFN-gamma, and suggests that Th1 and IL-17(+) T cells may collaboratively contribute to human autoimmune diseases.
引用
收藏
页码:4733 / 4741
页数:9
相关论文
共 53 条
[1]   Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells [J].
Acosta-Rodriguez, Eva V. ;
Napolitani, Giorgio ;
Lanzavecchia, Antonio ;
Sallusto, Federica .
NATURE IMMUNOLOGY, 2007, 8 (09) :942-949
[2]   Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].
Aggarwal, S ;
Ghilardi, N ;
Xie, MH ;
de Sauvage, FJ ;
Gurney, AL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914
[3]   Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-γ- and interleukin-4-induced activation of human keratinocytes [J].
Albanesi, C ;
Scarponi, CS ;
Cavani, A ;
Federici, M ;
Nasorri, F ;
Girolomoni, G .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 115 (01) :81-87
[4]   Serum levels of TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17 and IL-18 in patients with active psoriasis and correlation with disease severity [J].
Arican, O ;
Aral, M ;
Sasmaz, S ;
Ciragil, P .
MEDIATORS OF INFLAMMATION, 2005, (05) :273-279
[5]   TH-17 cells in the circle of immunity and autoimmunity [J].
Bettelli, Estelle ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2007, 8 (04) :345-350
[6]  
Betti M, 2006, ANN ONCOL, V17, P235
[7]   Innate immunity and antimicrobial defense systems in psoriasis [J].
Buchau, Amanda S. ;
Gallo, Richard L. .
CLINICS IN DERMATOLOGY, 2007, 25 (06) :616-624
[8]   A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes [J].
Cargill, Michele ;
Schrodi, Steven J. ;
Chang, Monica ;
Garcia, Veronica E. ;
Brandon, Rhonda ;
Callis, Kristina P. ;
Matsunami, Nori ;
Ardlie, Kristin G. ;
Civello, Daniel ;
Catanese, Joseph J. ;
Leong, Diane U. ;
Panko, Jackie M. ;
McAllister, Linda B. ;
Hansen, Christopher B. ;
Papenfuss, Jason ;
Prescott, Stephen M. ;
White, Thomas J. ;
Leppert, Mark F. ;
Krueger, Gerald G. ;
Begovich, Ann B. .
AMERICAN JOURNAL OF HUMAN GENETICS, 2007, 80 (02) :273-290
[9]   A novel method for the isolation of skin resident T cells from normal and diseased human skin [J].
Clark, Rachael A. ;
Chong, Benjamin F. ;
Mirchandani, Nina ;
Yamanaka, Kei-Ichi ;
Murphy, George F. ;
Dowgiert, Rebecca K. ;
Kupper, Thomas S. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (05) :1059-1070
[10]   α1β1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis [J].
Conrad, Curdin ;
Boyman, Onur ;
Tonel, Giulia ;
Tun-Kyi, Adrian ;
Laggner, Ute ;
de Fougerolles, Antonin ;
Kotelianski, Victor ;
Gardner, Humphrey ;
Nestle, Frank O. .
NATURE MEDICINE, 2007, 13 (07) :836-842