Cell:肠道Treg如何发生母婴传递?
创作:mildbreeze 审核:mildbreeze 06月01日
  • RORγ+ Treg在结肠Treg中的占比在不同小鼠品系间存在差异,能通过母系发生多代传递;
  • RORγ+ Treg的“设定值”主要取决于小鼠生命早期的养母(而非遗传、表观遗传或特定菌群),并在之后保持稳定,抵抗菌群和细胞因素的扰动;
  • 肠道IgA的产生及其包被共生菌的水平,与RORγ+ Treg负相关,且也能发生母系传递;
  • 孕晚期母鼠肠道的产IgA浆细胞增多,且能从肠道迁移至乳腺,通过乳汁IgA影响仔鼠肠内的IgA水平,决定了仔鼠RORγ+ Treg数量。
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mildbreeze
免疫存在遗传性,但这种遗传性并不局限于基因,近年研究表明表观遗传和菌群也参与其中。结肠中,表达RORγ的调节性T细胞(RORγ+ Treg)有控制炎症、抑制自身免疫反应等重要作用,这些细胞在生命早期可被细菌抗原诱导分化,然而,菌群的这种诱导作用似乎存在一个设定好的范围和天花板。这种“设定值”是如何产生的?《Cell》最新发表了来自哈佛医学院的重磅研究,在小鼠中揭示了决定稳态下的结肠RORγ+ Treg数量的一种跨代传递模式,能通过母亲传给后代。机制上,肠道中的RORγ+ Treg与IgA之间存在彼此抑制的关系,母鼠的RORγ+ Treg“设定值”能通过肠-乳腺轴反映在乳汁IgA含量上,从而通过乳汁IgA影响仔鼠肠道中IgA对共生菌的结合情况,进而决定了仔鼠的RORγ+ Treg数量。几个月前Nature发表的一项研究,报道了母鼠菌群诱导的IgG能通过母乳传递并保护后代抵抗感染(查看文章),这两项研究对于深入理解免疫的母婴传递,特别是母源抗体和“肠-乳腺轴”的作用,有重要参考价值。
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Cell [IF:36.216]

An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint

多代传递的免疫模式,控制肠道Treg设定点

10.1016/j.cell.2020.04.030

05-12, Article

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At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORγ-expressing regulatory T cells (Tregs) is essential in controlling gut inflammation. We uncovered a non-genetic, non-epigenetic, non-microbial mode of transmission of their homeostatic setpoint. RORγ + Treg proportions varied between inbred mouse strains, a trait transmitted by the mother during a tight age window after birth but stable for life, resistant to many microbial or cellular perturbations, then further transferred by females for multiple generations. RORγ + Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORγ + Treg-dependent manner. We propose a model based on a double-negative feedback loop, vertically transmitted via the entero-mammary axis. This immunologic mode of multi-generational transmission may provide adaptability and modulate the genetic tuning of gut immune responses and inflammatory disease susceptibility.

First Authors:
Deepshika Ramanan

Correspondence Authors:
Diane Mathis,Christophe Benoist

All Authors:
Deepshika Ramanan,Esen Sefik,Silvia Galván-Peña,Meng Wu,Liang Yang,Zhen Yang,Aleksandar Kostic,Tatyana V Golovkina,Dennis L Kasper,Diane Mathis,Christophe Benoist

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