RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity&IT In Vivo&IT

被引：20

作者：

Fuellel, Lorenz ^{[1
]}

Steiner, Nancy ^{[1
]}

Funke, Markus ^{[2
,3
]}

Gondorf, Fabian ^{[1
]}

Pfeiffer, Franziska ^{[2
,3
]}

Sieg, Julia ^{[2
,3
]}

Opitz, Friederike V. ^{[1
]}

Hassel, Silvana K. ^{[2
,3
]}

Erazo, Anna Belen ^{[1
]}

Schanz, Oliver ^{[1
]}

Stunden, H. James ^{[4
]}

Blank, Michael ^{[5
]}

Groeber, Carsten ^{[5
]}

Haendler, Kristian ^{[6
,7
,8
]}

Beyer, Marc ^{[6
,7
,8
,9
]}

Weighardt, Heike ^{[1
]}

Latz, Eicke ^{[4
]}

Schultze, Joachim L. ^{[6
,7
,8
]}

Mayer, Guenter ^{[2
,3
]}

Foerster, Irmgard ^{[1
]}

机构：

[1] Univ Bonn, Immunol & Environm Life & Med Sci LIMES Inst, Carl Troll Str 31, D-53115 Bonn, Germany

[2] Univ Bonn, Chem Biol & Chem Genet Life & Med Sci LIMES Inst, Gerhard Domagk Str 1, D-53121 Bonn, Germany

[3] Univ Bonn, Ctr Aptamer Res & Dev, Gerhard Domagk Str 1, D-53121 Bonn, Germany

[4] Univ Hosp Bonn, Inst Innate Immun, Sigmund Freud Str 25, D-53127 Bonn, Germany

[5] AptaIT, Klopferspitz 19a, D-82152 Planegg Martinsried, Germany

[6] Univ Bonn, Genom & Immunoregulat Life & Med Sci LIMES Inst, Carl Troll Str 31, D-53115 Bonn, Germany

[7] German Ctr Neurodegenerat Dis DZNE, Platform Single Cell Genom & Epigen, Sigmund Freud Str 27, D-53127 Bonn, Germany

[8] Univ Bonn, Sigmund Freud Str 27, D-53127 Bonn, Germany

[9] German Ctr Neurodegenerat Dis DZNE, Mol Immunol Neurodegenerat, Sigmund Freud Str 27, D-53127 Bonn, Germany

来源：

MOLECULAR THERAPY | 2018年 / 26卷 / 01期

关键词：

CHEMOKINE RECEPTOR CCR4; ACTIVATION-REGULATED CHEMOKINE; DENDRITIC CELLS; IMMUNE EVENTS; IN-VIVO; INFLAMMATION; DERMATITIS; LYMPHOMA; LIGANDS; THYMUS;

D O I：

10.1016/j.ymthe.2017.10.005

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4(+) lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner. To study the effect of these aptamers in vivo, we used a murine model of contact hyper-sensitivity. Systemic application of the aptamers significantly prevented ear swelling and T cell infiltration into the ears of sensitized mice after challenge with the contact sensitizer. The results of this proof-of-principle study establish aptamers as potent inhibitors of CCL17-mediated chemotaxis. Potentially, CCL17-specific aptamers maybe used therapeutically in humans to treat or prevent allergic and inflammatory diseases.

引用

页码：95 / 104

页数：10

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