J Autoimmun:磷酸酶控制细胞因子介导的半乳糖缺陷型IgA1(IgA肾病的主要自身抗原)过量产生

2022-09-04 彼岸河边草 MedSci原创

由于细胞因子介导的信号传导异常调节,IgA1分泌细胞的特定亚群可能负责IgA肾病中半乳糖缺陷型 IgA1 (Gd-IgA1) 自身抗原的产生,这一过程可能发生在 IgA肾病患者的炎症反应中。

 

背景:IgA肾病 (IgAN)是一种自身免疫性疾病,其特征是含有半乳糖缺陷型 IgA1 (Gd-IgA1) 的免疫复合物在肾脏中沉积。 IgAN中的主要自身抗原Gd-IgA1血清水平升高与IgAN患者的粘膜感染和肾脏预后不良有关,但对过度产生这种自身抗原的IgA1分泌细胞的激活知之甚少。

方法和结果:研究团队发现,在外周血单个核细胞(PBMC) 中,细胞因子刺激提高了IgAN患者B细胞中 Gd-IgA1的产生,但健康对照组的B细胞中没有(p < 0.01。这些结果在源自IgAN患者和健康对照的PBMC的永生化B细胞中得到了复制。使用单细胞转录组学,确定了来自IgAN患者的IgA1分泌细胞亚群,而不是来自健康对照的细胞亚群,其中C1GALT1的表达降低了对细胞因子刺激的反应。C1GALT1编码的糖基转移酶负责将半乳糖添加到 IgA1 O-聚糖上,其活性降低与Gd-IgA1血清水平升高有关。这些新发现的具有降低的 C1GALT1表达的IgA1分泌细胞亚群表现出与细胞因子介导的信号传导相关的几个基因的表达降低,包括那些编码磷酸酶的基因,例如SOCS1SOCS1和相关SOCS3siRNA敲低增加了来自健康对照 PBMC 的细胞中Gd-IgA1 的产生,表明这些调节剂在异常细胞因子信号传导和Gd-IgA1过度产生中的作用。

结论:以上这些结果表明,由于细胞因子介导的信号传导异常调节,IgA1分泌细胞的特定亚群可能负责IgAN中自身抗原的产生,这一过程可能发生在 IgAN 患者的炎症反应中。

出处:Reily C, Rice T, Crossman DK, Rizk DV. Phosphatase control of cytokine-mediated overproduction of galactose-deficient IgA1, the main autoantigen in IgA nephropathy. J Autoimmun. 2022 Aug 17;132:102883. doi: 10.1016/j.jaut.2022.102883. Epub ahead of print. PMID: 35987175.

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    2022-10-05 ms1000001920876216

    受益

    0

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03 10:06:04 CST 2022, time=2022-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1623442, encodeId=a46d1623442b2, content=<a href='/topic/show?id=62a655263e9' target=_blank style='color:#2F92EE;'>#抗原#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55263, encryptionId=62a655263e9, topicName=抗原)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f59b20519025, createdName=xiaoyeshuang, createdTime=Sat Sep 03 10:06:04 CST 2022, time=2022-09-03, status=1, ipAttribution=)]
    2022-09-04 yangchou

    好文章,谢谢分享。

    0

  5. 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  6. 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03 10:06:04 CST 2022, time=2022-09-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1623442, encodeId=a46d1623442b2, content=<a href='/topic/show?id=62a655263e9' target=_blank style='color:#2F92EE;'>#抗原#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55263, encryptionId=62a655263e9, topicName=抗原)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f59b20519025, createdName=xiaoyeshuang, createdTime=Sat Sep 03 10:06:04 CST 2022, time=2022-09-03, status=1, ipAttribution=)]
    2022-09-03 yibei
  8. 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  9. [GetPortalCommentsPageByObjectIdResponse(id=1810838, encodeId=805218108387f, content=<a href='/topic/show?id=5af886363e5' target=_blank style='color:#2F92EE;'>#自身抗原#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86363, encryptionId=5af886363e5, topicName=自身抗原)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=47c5349, createdName=tastas, createdTime=Wed Feb 22 22:06:04 CST 2023, time=2023-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2091964, encodeId=f674209196426, content=受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3fc8347029, createdName=ms1000001920876216, createdTime=Wed Oct 05 21:33:27 CST 2022, time=2022-10-05, status=1, 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  10. 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在西方国家,肥胖和动脉粥样硬化相关疾病占死亡率的1/3,其分子机制仍然不完全清楚。近日,新加坡研究人员发现敲除Wip1磷酸酶基因可改善肥胖和动脉粥样硬化。研究论文发表在7月3日的Cell Metabolism杂志上。 Wip1磷酸酶是Atm信号途径中的一个分子,它在脂肪聚集和动脉硬化中发挥重要作用,Wip1敲除的小鼠肥胖和动脉粥样硬化都得到改善。研究发现,Wip1磷酸酶可促进体重的上升和脂肪的累

Oncogene:肌醇聚磷酸酯4-磷酸酶II型调控雄激素受体的活性

晚期前列腺癌中AR的激活和转录重组总是与2个肿瘤抑制因子,INPP4B和PTEN的功能丧失同时发生,上述2个肿瘤抑制因子在人类和小鼠前列腺上皮中高表达。虽然AR信号通过PTEN的调控已经被多个研究组阐释,但是否INPP4B功能的丧失影响AR的活性仍旧不清楚。最近,有研究人员利用前列腺癌细胞系,展示了INPP4B能够调控AR转录活性和致瘤信号途径Akt和PKC。在前列腺癌患者群体中基因表达的分析表明

Cell:剑桥科学家“智擒”磷酸酶,造福罕见病患者

磷酸酶包括酸性和碱性两种。医生可通过测试体内这两种酶确定检测癌症等特定疾病。在之前的药性研究中,磷酸酶一直被认为不具有成药性(undruggable),但近日Cell一项研究称,科学家们开发出了一种可靶向磷酸酶的系统,并在小鼠实验中成功验证。这项发现让他们有机会筛选出靶向特定磷酸酶的药物。

Blood:过氧化氢酶低表达导致CLL的氧化还原反应超敏,并揭示其一种临床惰性行为

B细胞受体(BCR)信号是改变临床行为的关键因素,也是慢性淋巴细胞白血病(CLL)治疗干预的靶点。内源性H2O2是认为可通过可逆性抑制磷酸酶从而微调BCR信号。但是,目前对CLL细胞是如何感知并响应这类氧化还原信号,以及其对CLL的影响知之甚少。近日,Blood上发表一篇对此进行相关研究的文章。研究人员采用磷酸盐特异性流式细胞术,对CLL患者细胞内的BCR信号蛋白对外源性H2O2的反应性进行评估。

Nature:除了抗PD-1,还可以通过磷酸酶募集来抑制免疫受体

拮抗细胞外受体-配体相互作用的抗体可以抑制细胞表面受体的信号传递,目前广泛应用于包括肿瘤在内的多种疾病的治疗。比如,共受体(如PD-1和CTLA-4)对T细胞信号的调节一直是肿瘤免疫治疗的关键。