Maternal High Fiber Diet during Pregnancy and Lactation Influences Regulatory T Cell Differentiation in Offspring in Mice
Maternal High Fiber Diet during Pregnancy and Lactation Influences Regulatory T Cell Differentiation in Offspring in Mice
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DOI：
10.4049/jimmunol.1700248
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发表时间：
2017-11-15
影响因子：
4.4
通讯作者：
Watanabe, Sumio
中科院分区：
文献类型：
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作者：
Nakajima, Akihito;Kaga, Naoko;Watanabe, Sumio
短链脂肪酸(SCFAs)是膳食纤维的最终产物，影响免疫系统。此外，在怀孕期间，母亲的微生物群对后代的免疫系统的发育有很大的影响。然而，母体在妊娠和哺乳期影响子代免疫系统的确切机制尚不完全清楚。我们研究了母体高纤维饮食(HFD)调节子代T细胞(T-reg)分化的分子机制。饲喂高脂饮食小鼠的子代血浆中SCFAs水平高于不饲喂纤维饲料的小鼠。因此，饲喂HFD的小鼠的后代具有更高的胸腺T-reg(TT(Reg))和外周T-regs的频率。我们发现，饲喂HFD的小鼠后代表现出更高的自身免疫调节因子(Aire)的表达，这表明SCFA通过增加Aire的表达来促进TT(Reg)的分化。值得注意的是，丁酸受体，G蛋白偶联受体41(Gpr41)，在胸腺微环境中高表达，在Gpr41缺乏的小鼠中，丁酸刺激不会增加Aire的表达。我们的研究强调了母体HFD产生的SCFAs对于子代胸腺T-reg分化的重要性。鉴于Aire的表达与TT(Regs)的诱导有关，母体微生物群通过Gpr41介导的Aire表达影响子代胸腺T-reg的分化。
Short-chain fatty acids (SCFAs), the end products of dietary fiber, influence the immune system. Moreover, during pregnancy the maternal microbiome has a great impact on the development of the offspring's immune system. However, the exact mechanisms by which maternal SCFAs during pregnancy and lactation influence the immune system of offspring are not fully understood. We investigated the molecular mechanisms underlying regulatory T cell (T-reg) differentiation in offspring regulated by a maternal high fiber diet (HFD). Plasma levels of SCFAs in offspring from HFD-fed mice were higher than in those from no fiber diet-fed mice. Consequently, the offspring from HFD-fed mice had higher frequencies of thymic T-reg (tT(reg)) and peripheral T-regs. We found that the offspring of HFD-fed mice exhibited higher autoimmune regulator (Aire) expression, a transcription factor expressed in the thymic microenvironment, suggesting SCFAs promote tT(reg) differentiation through increased Aire expression. Notably, the receptor for butyrate, G protein-coupled receptor 41 (GPR41), is highly expressed in the thymic microenvironment and Aire expression is not increased by stimulation with butyrate in GPR41-deficient mice. Our studies highlight the significance of SCFAs produced by a maternal HFD for T-reg differentiation in the thymus of offspring. Given that Aire expression is associated with the induction of tT(regs), the maternal microbiome influences T-reg differentiation in the thymus of offspring through GPR41-mediated Aire expression.