Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides

被引:91
作者
Akdis, CA
Kussebi, F
Pulendran, B
Akdis, M
Lauener, RP
Schmidt-Weber, CB
Klunker, S
Isitmangil, G
Hansjee, N
Wynn, TA
Dillon, S
Erb, P
Baschang, G
Blaser, K
Alkan, SS
机构
[1] Swiss Inst Allergy & Asthma Res, CH-7270 Davos, Switzerland
[2] Emory Vaccine Res Ctr, Atlanta, GA USA
[3] Univ Zurich, Childrens Hosp, Zurich, Switzerland
[4] Yeditepe Univ, Sch Med, Istanbul, Turkey
[5] Univ Basel, Inst Med Microbiol, Basel, Switzerland
[6] NIH, Immunobiol Sect, Bethesda, MD 20892 USA
[7] Novartis Pharmaceut, Dept Chem, Basel, Switzerland
[8] Novartis Pharmaceut, Dept Resp Dis, Basel, Switzerland
关键词
allergy; T cells; IgE; lipopeptide; toll-like receptor 2;
D O I
10.1002/eji.200323329
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In allergy and asthma, the fine balance between the T helper (Th) 1, Th2 and T regulatory cytokine responses appears to be shifted towards Th2. Here, we report that synthetic lipopeptides which contain the typical lipid part of the lipoprotein of gram-negative bacteria stimulate a distinct regulatory cytokine pattern and inhibit several Th2 cell-related phenomena. The most potent analogue of synthetic lipopeptides, lipopeptide CGP 40774 (LP40) was not active in MyD88-deficient mice and stimulated Toll-like receptor (TLR)-2, but not TLR-4. LP40 potentiated the production of IFN-gamma and IL-10, but not IL-4 and IL-5 by human T cells. In addition, triggering of TLR-2 by lipopeptides promoted the in vitro differentiation of naive T cells towards IL-10- and IFN-gamma-producing T cells and suppressed IL-4 production by Th2 cells. Accordingly, LP40 inhibited IgE production induced by allergen, anti-IgD antibody, Nippostrongylus brasiliensis or murine acquired immunodeficiency virus. Furthermore, ovalbumin-induced lung eosinophilic inflammation was abolished and Schistosoma mansoni egg-induced granuloma size and eosinophil counts were suppressed in mice by LP40. These results demonstrate that stimulation of TLR-2 by lipopeptides represents a novel way for possible treatment of allergy and asthma by regulating the disrupted cytokine balance.
引用
收藏
页码:2717 / 2726
页数:10
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