Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis.
Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis.
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DOI：
10.1161/hypertensionaha.122.19307
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发表时间：
2022-10
期刊：
影响因子：
8.3
通讯作者：
Vijay-Kumar, Matam
中科院分区：
文献类型：
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作者：
Saha, Piu;Mell, Blair;Golonka, Rachel M.;Bovilla, Venugopal R.;Abokor, Ahmed A.;Mei, Xue;Yeoh, Beng San;Doris, Peter A.;Gewirtz, Andrew T.;Joe, Bina;Vijay-Kumar, Matam
自发性高血压大鼠（SHR）广泛用于研究高血压。肠道菌群失调是 SHR 的一个显着特征，原因未知。免疫球蛋白 A (IgA) 是肠道微生物群稳态所需的主要宿主因子。我们假设 IgA 不足会导致 SHR 肠道菌群失调。在 SHR 和 Wistar京都 (WKY) 大鼠的粪便、盲肠、血清、肝脏、肠道相关淋巴组织和乳汁中测量了 IgA。分析了 IgM、IgG 和聚合免疫球蛋白受体 (pIgR) 等 IgA 调节因子。在施用细菌抗原（即鞭毛蛋白）之前和之后测量 IgA 和 IgG 抗体以及血压 (BP)。与 WKY 大鼠相比，SHR 显示出明显接近缺陷的 IgA 水平，同时血清 IgM 和 IgG 以及肠肝 pIgR 表达代偿性增加。 SHR 中乳汁 IgA 不足强调了这种免疫缺陷源于新生儿阶段。循环中 IgA+ B 细胞和派尔氏集结的减少表明 SHR 中 IgA 较低的可能原因。值得注意的是，遗传缺陷不太可能，因为向 SHR 施用鞭毛蛋白会诱导抗鞭毛蛋白 IgA 抗体。这种免疫反应令人惊讶地加速了 SHR 中高血压的发展，表明 IgA 静止可能有助于维持较低的血压。这项研究首次揭示了 SHR 中 IgA 缺乏是与肠道菌群失调相关的一个宿主因素，并为未来确定 IgA 在高血压中的病理生理学作用的研究注入了活力。
The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR. IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue and milk from SHR and Wistar Kyoto (WKY) rats. IgA regulatory factors like IgM, IgG and polymeric immunoglobulin receptor (pIgR) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after adminstrating a bacterial antigen (i.e., flagellin). Compared to WKY rats, SHR displayed remarkably near-deficient IgA levels accompanied with compensatory increases in serum IgM and IgG and gut-liver pIgR expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+ B cells in circulation and Peyer’s patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP. This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
DOI：
10.1016/j.jpeds.2017.04.005
发表时间：
2017-08
期刊：
The Journal of pediatrics
影响因子：
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作者：
Locks LM;Mwiru RS;Mtisi E;Manji KP;McDonald CM;Liu E;Kupka R;Kisenge R;Aboud S;Gosselin K;Gillman M;Gewirtz AT;Fawzi WW;Duggan CP
通讯作者：
Duggan CP