Neurotophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

被引：12

作者：

Bandola, Joanna ^{[1
]}

Richter, Cornelia ^{[1
]}

Ryser, Martin ^{[1
]}

Jamal, Arshad ^{[1
,2
]}

Ashton, Michelle P. ^{[3
]}

von Bonin, Malte ^{[4
,5
,6
]}

Kuhn, Matthias ^{[7
]}

Dorschner, Benjamin ^{[1
]}

Alexopoulou, Dimitra ^{[8
]}

Navratiel, Katrin ^{[1
]}

Roeder, Ingo ^{[7
]}

Dahl, Andreas ^{[8
]}

Hedrich, Christian M. ^{[1
]}

Bonifacio, Ezio ^{[3
]}

Brenner, Sebastian ^{[1
,3
]}

Thieme, Sebastian ^{[1
]}

机构：

[1] Univ Clin Dresden, Dept Pediat, Dresden, Germany

[2] Imperial Coll Business Studies, Dept Med Lab Sci, Lahore, Pakistan

[3] Tech Univ Dresden, DFG Ctr Regenerat Therapies Dresden, Cluster Excellence, Dresden, Germany

[4] Univ Clin Dresden, Med Clin 1, Dresden, Germany

[5] Univ Clin Dresden, DKTK German Canc Consortium, Partner Site Dresden, Dresden, Germany

[6] DKFZ German Canc Res Ctr, Heidelberg, Germany

[7] Tech Univ Dresden, Inst Med Informat & Biometry, Fac Med, Dresden, Germany

[8] Tech Univ Dresden, DFG Ctr Regenerat Therapies Dresden, BIOTEChnol Ctr, Cluster Excellence, Dresden, Germany

来源：

FRONTIERS IN IMMUNOLOGY | 2017年 / 8卷

关键词：

plasmacytoid dendritic cells; p75 neurotrophin receptor; neurotrophin; TLR; 9; autoimmune diabetes; graft-versus-host disease; allergic asthma; NERVE-GROWTH-FACTOR; BRONCHOALVEOLAR LAVAGE FLUID; VERSUS-HOST-DISEASE; NEUROTROPHIN RECEPTOR; AIRWAY INFLAMMATION; IN-VITRO; T-CELLS; INTRAMEMBRANE PROTEOLYSIS; ACTIVATION; EXPRESSION;

D O I：

10.3389/fimmu.2017.00981

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

引用

页数：16

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