Gut bacteria-derived serotonin promotes immune tolerance in early life

被引:20
作者
Sanidad, Katherine Z. [1 ,2 ]
Rager, Stephanie L. [2 ,9 ]
Carrow, Hannah C. [1 ,2 ,3 ]
Ananthanarayanan, Aparna [1 ,2 ]
Callaghan, Ryann [3 ]
Hart, Lucy R. [1 ,2 ]
Li, Tingting [4 ]
Ravisankar, Purnima [1 ,2 ,3 ]
Brown, Julia A. [1 ,2 ]
Amir, Mohammed [1 ,2 ]
Jin, Jenny C. [1 ,2 ]
Savage, Alexandria Rose [5 ]
Luo, Ryan [1 ]
Rowdo, Florencia Mardorsky [6 ]
Martin, M. Laura [6 ]
Silver, Randi B. [5 ]
Guo, Chun-Jun [4 ]
Krumsiek, Jan [7 ]
Inohara, Naohiro [8 ]
Zeng, Melody Y. [1 ,2 ,3 ]
机构
[1] Weill Cornell Med, Gale & Ira Drukier Inst Childrens Hlth, New York, NY 10065 USA
[2] Weill Cornell Med, Dept Pediat, New York, NY 10065 USA
[3] Weill Cornell Grad Sch, Immunol & Microbial Pathogenesis Program, New York, NY 10065 USA
[4] Weill Cornell Med, Jill Roberts Inst Res Inflammatory Bowel Dis, New York, NY 10065 USA
[5] Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA
[6] Weill Cornell Med, Englander Inst Precis Med, New York, NY 10065 USA
[7] Weill Cornell Med, Inst Computat Biomed, New York, NY 10065 USA
[8] Univ Michigan, Rogel Canc Ctr, Ann Arbor, MI 48109 USA
[9] Columbia Univ, Vagelos Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA
关键词
ORAL TOLERANCE; STRESS-RESPONSE; MICROBIOTA; COLONIZATION; BEHAVIOR; SYSTEM;
D O I
10.1126/sciimmunol.adj4775
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine. Oral gavage of serotonin into neonatal mice resulted in long-term T cell-mediated antigen-specific immune tolerance toward both dietary antigens and commensal bacteria. Together, our study has uncovered an important role for specific gut bacteria to increase serotonin availability in the neonatal gut and identified a function of gut serotonin in shaping T cell response to dietary antigens and commensal bacteria to promote immune tolerance in early life.
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页数:15
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