An epithelial cell-derived metabolite tunes immunoglobulin A secretion by gut-resident plasma cells.
An epithelial cell-derived metabolite tunes immunoglobulin A secretion by gut-resident plasma cells.
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DOI：
10.1038/s41590-022-01413-w
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发表时间：
2023-03
影响因子：
30.5
通讯作者：
Reboldi, Andrea
中科院分区：
文献类型：
--
作者：
Ceglia, Simona;Berthelette, Alyssa;Howley, Kelsey;Li, Yun;Mortzfeld, Benedikt;Bhattarai, Shakti K.;Yiew, Nicole K. H.;Xu, Ying;Brink, Robert;Cyster, Jason G.;Hooper, Lora V.;Randolph, Gwendalyn J.;Bucci, Vanni;Reboldi, Andrea
免疫球蛋白A(IgA)由浆细胞分泌，位于肠道固有层中，是终末分化的B细胞，确保微生物群的动态平衡，保护宿主免受肠道感染。暴露于饮食来源和共生组织来源的信号为免疫细胞提供了组织线索，这些线索指示它们的效应器功能，并在粘膜屏障处动态塑造肠道免疫反应。最近的数据已经描述了控制肠道内T细胞和固有淋巴样细胞激活的代谢和微生物输入；然而，分泌IgA的固有层浆细胞是否受到局部刺激的调节完全未知。虽然抗体分泌被认为是在B细胞分化过程中印记的，因此在很大程度上不受环境变化的影响，但对肠道波动的快速调节对宿主可能是有利的。在这里，我们展示了饮食中胆固醇的吸收和十二指肠肠上皮细胞的共生识别导致氧固醇的产生，这是进化上保守的具有免疫调节功能的脂类。利用条件性CH25H缺失小鼠，我们证明了来自上皮细胞的7a，25-HC对于抑制肠道内针对共生抗原和病原体来源的抗原的IgA分泌是关键的。肠道浆细胞通过趋化受体GPR183感知氧合甾醇，并将其组织定位与IgA分泌相结合。我们的发现揭示了一种新的机制，将饮食中的胆固醇和体液免疫反应联系在一起，以浆细胞定位为中心，以有效的粘膜保护。
Immunoglobulin A (IgA) secretion by plasma cells, terminally differentiated B cells residing in the intestinal lamina propria, assures microbiome homeostasis and protects the host against enteric infections. Exposure to diet-derived and commensal-derived signals provides immune cells with organizing cues that instruct their effector function and dynamically shape intestinal immune responses at the mucosal barrier. Recent data have described metabolic and microbial inputs controlling T cell and innate lymphoid cell activation in the gut; however, whether IgA-secreting lamina propria plasma cells are tuned by local stimuli is completely unknown. While antibody secretion is considered to be imprinted during B cell differentiation and therefore largely unaffected by environmental changes, a rapid modulation of IgA levels in response to intestinal fluctuations might be beneficial to the host. Here we showed that dietary cholesterol absorption and commensal recognition by duodenal intestinal epithelial cells lead to the production of oxysterols, evolutionarily conserved lipids with immunomodulatory functions. Using conditional CH25H deleter mouse line we demonstrated that 7a,25-HC from epithelial cells is critical to restrain IgA secretion against commensal and pathogen-derived antigens in the gut. Intestinal plasma cells sense oxysterols via the chemoattractant receptor GPR183 and couple their tissue positioning with IgA secretion. Our findings revealed a new mechanism linking dietary cholesterol and humoral immune responses centered around plasma cell localization for efficient mucosal protection.
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餐后乳糜微粒的输出和通过肠道淋巴管的运输在活跃的克罗恩病中不会受到损害。
影响因子：
29.4
作者：
Huang LH;Deepak P;Ciorba MA;Mittendorfer B;Patterson BW;Randolph GJ
通讯作者：
Randolph GJ
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1073/pnas.0909142106
发表时间：
2009-09-29
影响因子：
11.1
作者：
Bauman, David R.;Bitmansour, Andrew D.;Russell, David W.
通讯作者：
Russell, David W.
影响因子：
4.8
作者：
Davis, HR;Zhu, LJ;Altmann, SW
通讯作者：
Altmann, SW
DOI：
10.1084/jem.20111980
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lindner C;Wahl B;Föhse L;Suerbaum S;Macpherson AJ;Prinz I;Pabst O
通讯作者：
Pabst O