Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells

被引：366

作者：

Heink, Sylvia ^{[1
]}

Yogev, Nir ^{[2
,13
]}

Garbers, Christoph ^{[3
]}

Herwerth, Marina ^{[1
,4
]}

Aly, Lilian ^{[1
]}

Gasperi, Christiane ^{[1
]}

Husterer, Veronika ^{[1
]}

Croxford, Andrew L. ^{[2
]}

Moeller-Hackbarth, Katja ^{[3
]}

Bartsch, Harald S. ^{[5
]}

Sotlar, Karl ^{[5
]}

Krebs, Stefan ^{[6
]}

Regen, Tommy ^{[2
]}

Blum, Helmut ^{[6
]}

Hemmer, Bernhard ^{[1
,7
]}

Misgeld, Thomas ^{[4
,7
]}

Wunderlich, Thomas F. ^{[8
]}

Hidalgo, Juan ^{[9
]}

Oulcka, Mohamed ^{[10
,11
]}

Rose-John, Stefan ^{[3
]}

Schmidt-Supprian, Marc ^{[12
]}

Waisman, Ari ^{[2
]}

Korn, Thomas ^{[1
,7
]}

机构：

[1] Tech Univ Munich, Dept Neurol, Klinikum Rechts Isar, Munich, Germany

[2] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, Mainz, Germany

[3] Univ Kiel, Inst Biochem, Kiel, Germany

[4] Tech Univ Munich, Inst Neuronal Cell Biol, Munich, Germany

[5] Ludwig Maximilians Univ Munchen, Sch Med, Inst Pathol, Munich, Germany

[6] Ludwig Maximilians Univ Munchen, Gene Ctr, Lafuga, Munich, Germany

[7] Munich Cluster Syst Neurol SyNergy, Munich, Germany

[8] Max Planck Inst Metab Res, Cologne, Germany

[9] Autonomous Univ Barcelona, Dept Cellular Biol Physiol & Immunol, Barcelona, Spain

[10] Univ Washington, Dept Immunol, Seattle, WA 98195 USA

[11] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA

[12] Tech Univ Munich, Dept Hematol & Oncol, Klinikum Rechts Isar, Munich, Germany

[13] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Neurol, Mainz, Germany

来源：

NATURE IMMUNOLOGY | 2017年 / 18卷 / 01期

基金：

欧洲研究理事会;

关键词：

REGULATORY T-CELLS; SOLUBLE INTERLEUKIN-6; TH17; CELLS; TGF-BETA; GENERATION; CYTOKINES; DIFFERENTIATION; POPULATIONS; INHIBITION; INDUCTION;

D O I：

10.1038/ni.3632

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the T(H)17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirp alpha were essential for the generation of pathogenic T(H)17 cells. Using their IL-6 receptor a-chain (IL-6R alpha), Sirp alpha(+) DCs trans-presented IL-6 to T cells during the process of cognate interaction. While ambient IL-6 was sufficient to suppress the induction of expression of the transcription factor Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6R alpha (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-gamma (IFN-gamma) expression in T cells and to generate pathogenic T(H)17 cells in vivo. Our findings should guide therapeutic approaches for the treatment of T(H)17-cell-mediated autoimmune diseases.

引用

页码：74 / 85

页数：12

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