CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis

被引：28

作者：

Barthels, Christian ^{[1
]}

Ogrinc, Ana ^{[1
]}

Steyer, Verena ^{[1
]}

Meier, Stefanie ^{[1
]}

Simon, Ferdinand ^{[1
]}

Wimmer, Maria ^{[2
,3
]}

Blutke, Andreas ^{[4
]}

Straub, Tobias ^{[5
]}

Zimber-Strobl, Ursula ^{[6
]}

Lutgens, Esther ^{[7
,8
]}

Marconi, Peggy ^{[9
]}

Ohnmacht, Caspar ^{[2
,3
]}

Garzetti, Debora ^{[10
]}

Stecher, Baerbel ^{[10
]}

Brocker, Thomas ^{[1
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Inst Immunol, Grosshaderner Str 9, D-82152 Planegg Martinsried, Germany

[2] Helmholtz Ctr, Ctr Allergy Environm ZAUM, D-85764 Neuherberg, Germany

[3] Tech Univ Munich, D-85764 Neuherberg, Germany

[4] Ludwig Maximilians Univ Munchen, Sect Anim Pathol, Dept Vet Clin Sci, D-80539 Munich, Germany

[5] Ludwig Maximilians Univ Munchen, BMC, Bioinformat Core Unit, Grosshaderner Str 9, D-82152 Planegg Munich, Germany

[6] Helmholtz Zentrum Munchen, Res Unit Gene Vectors, D-81377 Munich, Germany

[7] Ludwig Maximilians Univ Munchen, Inst Prophylaxe & Epidemiol Kreislaufkrankheiten, D-80336 Munich, Germany

[8] AMC, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands

[9] Univ Ferrara, Dept Life Sci & Biotechnol, I-44121 Ferrara, Italy

[10] Ludwig Maximilians Univ Munchen, Partner Site Munich, German Ctr Infect Res DZIF, Max von Pettenkofer Inst Hyg & Med Microbiol, D-80336 Munich, Germany

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

欧洲研究理事会;

关键词：

REGULATORY T-CELLS; CLASSICAL DENDRITIC CELLS; IN-VIVO; INTEGRIN ALPHA-V-BETA-8; SIGNALING CONTROLS; RETINOIC-ACID; TH17; CELLS; REG-CELLS; B-CELLS; IMMUNITY;

D O I：

10.1038/ncomms14715

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103(+) dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan gamma t(+) (ROR gamma t(+)) Helios(-)-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103(+) DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103(+) DCs in LP and a low frequency of ROR gamma t(+)Helios(-) iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity.

引用

页数：12

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