Secretion of autoimmune antibodies in the human subcutaneous adipose tissue.
Secretion of autoimmune antibodies in the human subcutaneous adipose tissue.
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DOI：
10.1371/journal.pone.0197472
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Blomberg BB
中科院分区：
文献类型：
--
作者：
Frasca D;Diaz A;Romero M;Thaller S;Blomberg BB
脂肪组织（AT）有助于全身性和B细胞内在炎症、降低的B细胞应答和自身免疫抗体的分泌。在这项研究中，我们表明，在人类肥胖的皮下AT（SAT）的脂肪细胞分泌几种促炎细胞因子和趋化因子，这有助于建立和维持局部和全身炎症，以及随后的次优免疫反应在肥胖的个人，正如我们以前所示。我们还表明，促炎趋化因子招募免疫细胞表达相应的受体的SAT，在那里他们也有助于局部和全身炎症，分泌额外的促炎介质。此外，我们表明，SAT产生自身免疫抗体。在肥胖症的发展过程中，氧气减少和随之而来的缺氧和细胞死亡导致促炎细胞因子、“自身”蛋白抗原、无细胞DNA和脂质的进一步释放。所有这些刺激类别转换和已被描述为致病的自身免疫IgG抗体的产生。除了缺氧，我们还测量了细胞毒性和DNA损伤机制，这也可能有助于SAT中“自身”抗原的释放。与血液相比，所有这些过程在SAT中显著升高。我们明确发现，脂肪特异性IgG抗体由SAT中的B细胞分泌，并且B细胞表达转录因子T-bet和膜标记物CD 11 c的mRNA，这两者都参与自身免疫IgG抗体的产生。最后，SAT还表达已知促进生殖中心形成、同种型类别转换和浆细胞分化的细胞因子的RNA。我们的研究结果显示了在人类SAT中产生自身免疫抗体反应的新机制，并允许识别可能操纵的新途径，以减少肥胖个体的全身炎症和自身抗体产生。
The adipose tissue (AT) contributes to systemic and B cell intrinsic inflammation, reduced B cell responses and secretion of autoimmune antibodies. In this study we show that adipocytes in the human obese subcutaneous AT (SAT) secrete several pro-inflammatory cytokines and chemokines, which contribute to the establishment and maintenance of local and systemic inflammation, and consequent suboptimal immune responses in obese individuals, as we have previously shown. We also show that pro-inflammatory chemokines recruit immune cells expressing the corresponding receptors to the SAT, where they also contribute to local and systemic inflammation, secreting additional pro-inflammatory mediators. Moreover, we show that the SAT generates autoimmune antibodies. During the development of obesity, reduced oxygen and consequent hypoxia and cell death lead to further release of pro-inflammatory cytokines, “self” protein antigens, cell-free DNA and lipids. All these stimulate class switch and the production of autoimmune IgG antibodies which have been described to be pathogenic. In addition to hypoxia, we have measured cell cytotoxicity and DNA damage mechanisms, which may also contribute to the release of “self” antigens in the SAT. All these processes are significantly elevated in the SAT as compared to the blood. We definitively found that fat-specific IgG antibodies are secreted by B cells in the SAT and that B cells express mRNA for the transcription factor T-bet and the membrane marker CD11c, both involved in the production of autoimmune IgG antibodies. Finally, the SAT also expresses RNA for cytokines known to promote Germinal Center formation, isotype class switch, and plasma cell differentiation. Our results show novel mechanisms for the generation of autoimmune antibody responses in the human SAT and allow the identification of new pathways to possibly manipulate in order to reduce systemic inflammation and autoantibody production in obese individuals.
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影响因子：
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作者：
Henneken M;Dörner T;Burmester GR;Berek C
通讯作者：
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影响因子：
12.6
作者：
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影响因子：
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作者：
Havenith, Simone H. C.;Remmerswaal, Ester B. M.;van Lier, Rene A. W.
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van Lier, Rene A. W.
DOI：
10.1073/pnas.1215840110
发表时间：
2013-03-26
影响因子：
11.1
作者：
DeFuria, Jason;Belkina, Anna C.;Nikolajczyk, Barbara S.
通讯作者：
Nikolajczyk, Barbara S.