葡萄牙里斯本大學(xué)分子醫(yī)學(xué)研究所*的一個研究組在新研究中證實，相比于那些在子宮中暴露于高水平維生素的動物，低維生素飲食喂養(yǎng)的孕鼠后代發(fā)育的淋巴結(jié)較小。剝奪維生素的小鼠腸道中淋巴結(jié)樣結(jié)構(gòu)：Peyer’s結(jié)的數(shù)量也較少。遺傳操控使得*代謝產(chǎn)物*受體缺陷的鼠胚胎也是這種情況。出生后，正常的飲食不能逆轉(zhuǎn)子宮內(nèi)*缺乏所造成的影響，其似乎阻礙了小鼠對抗感染的能力，甚至在它們成年之后仍是如此。

以往針對第二淋巴器官發(fā)育進行研究的結(jié)果表明這一過程受到嚴格編程。當(dāng)前的研究*次提出了母親的行為可以改變這種發(fā)育。

荷蘭Erasmus 醫(yī)學(xué)中心免疫學(xué)家Tom Cupedo(未參與該研究) 說：“我們一直認為免疫系統(tǒng)器官發(fā)育是一個獨立自主的過程。但現(xiàn)在我認為，這篇論文表明了事實上孕婦的飲食可以影響免疫系統(tǒng)器官，以及由此影響免疫系統(tǒng)功能……形成。”

除了淋巴結(jié)的大小，科學(xué)家們還試圖調(diào)查*可能影響發(fā)育免疫系統(tǒng)的其他方面。在免疫系統(tǒng)發(fā)育過程中，帶有CD4標(biāo)記物的淋巴組織誘導(dǎo)細胞(LTi4)對于淋巴結(jié)和其他次級淋巴器官的形成至關(guān)重要。這些細胞不同于缺失CD4的另一種先天淋巴細胞類型ILC4neg。

研究人員發(fā)現(xiàn)，*影響了這些誘導(dǎo)細胞的分化。他們喂給孕鼠富含*的飲食，發(fā)現(xiàn)胚胎中LTi4細胞與ILC4neg細胞的比值增高。抑制*信號則具有相反的效應(yīng)。*受體突變的胚胎相比對照胚胎誘導(dǎo)細胞百分比下降。研究人員由此提出，*對于這些LTi4細胞分化至關(guān)重要。

在確定了出生后正常飲食不能逆轉(zhuǎn)子宮中剝奪*所造成的影響后，研究人員想知道骨髓移植是否可能獲得這一效應(yīng)。研究人員取得*受體突變的后代，將來自野生型小鼠的造血干細胞移植到它們體內(nèi)。這種移植也不能逆轉(zhuǎn)維生素缺乏所造成的影響。

即便移植干細胞，在子宮中暴露于低水平*的后代淋巴結(jié)較小，相比對照(移植同樣干細胞的野生型小鼠)它們對抗肺臟病毒感染能力較弱。Cupedo說：“我們過去總是認為這是二選一的過程——你或者形成淋巴結(jié)或不形成。現(xiàn)在證實了有一個中間體，淋巴結(jié)大小實際上影響了以后生活中抗感染免疫的發(fā)生。”

原文摘要：

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

Serge A. van de Pavert, Manuela Ferreira, Rita G. Domingues, Hélder Ribeiro, Rosalie Molenaar, Lara Moreira-Santos, Francisca F. Almeida, Sales Ibiza, Inês Barbosa, Gera Goverse, Carlos Labão-Almeida, Cristina Godinho-Silva, Tanja Konijn, Dennis Schooneman, Tom O’Toole, Mark R. Mizee, Yasmin Habani, Esther Haak, Fabio R. Santori,Dan R. Littman, Stefan Schulte-Merker, Elaine Dzierzak, J. Pedro Simas, Reina E. Mebius &Henrique Veiga-Fernandes

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcr-ption factor RORγt. Accordingly, enforced expressi0n of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular 1ink between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.