Proinflammatory T helper type 17 cells are effective B-cell helpers

被引:426
作者
Mitsdoerffer, Meike [2 ]
Lee, Youjin [2 ]
Jaeger, Anneli [2 ]
Kim, Hye-Jung [1 ]
Korn, Thomas [3 ]
Kolls, Jay K. [4 ]
Cantor, Harvey [1 ]
Bettelli, Estelle [5 ]
Kuchroo, Vijay K. [2 ]
机构
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
[3] Tech Univ Munich, Dept Neurol, D-81675 Munich, Germany
[4] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA
[5] Benaroya Res Inst, Seattle, WA 98101 USA
基金
美国国家卫生研究院;
关键词
germinal center; IL-17; immunoglobulin; isotype class switching; T helper cell; IN-VIVO; IL-21; DIFFERENTIATION; GENERATION; RESPONSES; PLASTICITY; RECEPTOR; LINEAGE; IL-17; TH1;
D O I
10.1073/pnas.1009234107
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
T helper type 17 (TH17) cells are highly proinflammatory effector T cells that are characterized by the production of high amounts of IL-17A, IL-17F, IL-21, and IL-22. Furthermore, TH17 cells have been associated with a number of autoimmune diseases. However, it is not clear whether TH17 cells can also serve as effective helper cells. Here we show that TH17 cells can function as B-cell helpers in that they not only induce a strong proliferative response of B cells in vitro but also trigger antibody production with class switch recombination in vivo. Transfer of TH17 cells into WT or T-cell receptor a-deficient mice, which lack endogenous T cells, induces a pronounced antibody response with preferential isotype class switching to IgG1, IgG2a, IgG2b, and IgG3, as well as the formation of germinal centers. Conversely, blockade of IL-17 signaling results in a significant reduction in both number and size of germinal centers. Whereas IL-21 is known to help B cells, IL-17 on its own drives B cells to undergo preferential isotype class switching to IgG2a and IgG3 subtypes. These observations provide insights into the unappreciated role of TH17 cells and their signature cytokines in mediating B-cell differentiation and class switch recombination.
引用
收藏
页码:14292 / 14297
页数:6
相关论文
共 36 条
[1]   The N-terminal domain of the myelin oligodendrocyte glycoprotein (MOG) induces acute demyelinating experimental autoimmune encephalomyelitis in the Lewis rat [J].
Adelmann, M ;
Wood, J ;
Benzel, I ;
Fiori, P ;
Lassmann, H ;
Matthieu, JM ;
Gardinier, MV ;
Dornmair, K .
JOURNAL OF NEUROIMMUNOLOGY, 1995, 63 (01) :17-27
[2]   The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells [J].
Bauquet, Aurelie T. ;
Jin, Hulin ;
Paterson, Alison M. ;
Mitsdoerffer, Meike ;
Ho, I-Cheng ;
Sharpe, Arlene H. ;
Kuchroo, Vijay K. .
NATURE IMMUNOLOGY, 2009, 10 (02) :167-175
[3]   Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis [J].
Bettelli, E ;
Pagany, M ;
Weiner, HL ;
Linington, C ;
Sobel, RA ;
Kuchroo, AK .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (09) :1073-1081
[4]   RETRACTED: Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus (Retracted Article) [J].
Doreau, Agnes ;
Belot, Alexandre ;
Bastid, Jeremy ;
Riche, Benjamin ;
Trescol-Biemont, Marie-Claude ;
Ranchin, Bruno ;
Fabien, Nicole ;
Cochat, Pierre ;
Pouteil-Noble, Claire ;
Trolliet, Pierre ;
Durieu, Isabelle ;
Tebib, Jacques ;
Kassai, Berhouz ;
Ansieau, Stephane ;
Puisieux, Alain ;
Eliaou, Jean-Francois ;
Bonnefoy-Berard, Nathalie .
NATURE IMMUNOLOGY, 2009, 10 (07) :778-U142
[5]   The role of IL-21 in regulating B-cell function in health and disease [J].
Ettinger, Rachel ;
Kuchen, Stefan ;
Lipsky, Peter E. .
IMMUNOLOGICAL REVIEWS, 2008, 223 :60-86
[6]   T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J].
Fossiez, F ;
Djossou, O ;
Chomarat, P ;
FloresRomo, L ;
AitYahia, S ;
Maat, C ;
Pin, JJ ;
Garrone, P ;
Garcia, E ;
Saeland, S ;
Blanchard, D ;
Gaillard, C ;
DasMahapatra, B ;
Rouvier, E ;
Golstein, P ;
Banchereau, J ;
Lebecque, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (06) :2593-2603
[7]   Structure and signalling in the IL-17 receptor family (vol 9, pg 556, 2009) [J].
Gaffen, Sarah L. .
NATURE REVIEWS IMMUNOLOGY, 2009, 9 (08) :556-567
[8]  
Han S, 1997, Semin Immunol, V9, P255, DOI 10.1006/smim.1997.0081
[9]   Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice [J].
Hsu, Hui-Chen ;
Yang, PingAr ;
Wang, John ;
Wu, Qi ;
Myers, Riley ;
Chen, Jian ;
Yi, John ;
Guentert, Tanja ;
Tousson, Albert ;
Stanus, Andrea L. ;
Le, Thuc-vy L. ;
Lorenz, Robin G. ;
Xu, Hui ;
Kolls, Jay K. ;
Carter, Robert H. ;
Chaplin, David D. ;
Williams, Robert W. ;
Mountz, John D. .
NATURE IMMUNOLOGY, 2008, 9 (02) :166-175
[10]   Differential Roles of Interleukin-17A and-17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses [J].
Ishigame, Harumichi ;
Kakuta, Shigeru ;
Nagai, Takeshi ;
Kadoki, Motohiko ;
Nambu, Aya ;
Komiyama, Yutaka ;
Fujikado, Noriyuki ;
Tanahashi, Yuko ;
Akitsu, Aoi ;
Kotaki, Hayato ;
Sudo, Katsuko ;
Nakae, Susumu ;
Sasakawa, Chihiro ;
Iwakura, Yoichiro .
IMMUNITY, 2009, 30 (01) :108-119