研究进展:细胞因子IL-10生物学和治疗潜力多样性详解

2021-07-02 义翘神州 义翘神州

细胞因子在免疫治疗领域有哪些具体的应用呢?

白细胞介素(Interleukin),简称白介素,存在于白细胞或免疫细胞间相互作用的细胞因子。目前已发现的人类基因组编码的白介素及相关蛋白种类超过50种,大多由辅助CD4 T细胞及单核细胞、巨噬细胞和内皮细胞产生。白介素在传递信息,激活与调节免疫细胞功能,介导T、B细胞活化、增殖,以及炎症反应等方面具有重要作用。白介素细胞因子一直是新药研发的热门靶点,收到国内外研发企业的“钟爱”。

白细胞介素10(IL-10),也称为细胞因子合成抑制因子(CSIF),是一种多效性细胞因子,可以在多种类型细胞中发挥免疫抑制或免疫刺激的作用。IL-10基因定位于染色体1q31-32上,主要由单核细胞、T细胞(主要是Th1细胞)、B细胞、NK细胞、巨噬细胞产生,DC细胞和肥大细胞也可以产生IL-10,但单核细胞和B细胞是人IL-10的主要来源。

IL-10属于同源二聚体分泌物,由2个亚基组成,分子量大小为18kd。IL-10受体由2个IL-10R1和2个IL-10R2链组成。当IL-10与受体复合物结合后,就会激活Janus激酶1(JAK1)和酪氨酸激酶2(TYK2),信号转导和转录激活因子STAT1、STAT3。还有一些其他的激酶也可以被激活,比如丝裂原活化蛋白激酶和血红素加氧酶-1。

参与IL-10调节的信号分子(外圈)和转录因子(内圈)

当IL-10与其细胞受体复合物IL-10R1/IL-10R2结合时,它开始发挥多种免疫抑制功能。通过阻止Th1细胞产生细胞因子,首次发现IL-10是一种细胞因子合成抑制因子。进一步的研究表明,IL-10还能抑制抗原呈递细胞(巨噬细胞和树突状细胞)的细胞因子产生能力,以及共刺激分子表达(CD80、CD86)。IL-10被认为是由许多不同种类的免疫细胞和组织上皮细胞产生的关键抗炎细胞因子。

IL-10功能性地靶向多种细胞,从而产生广泛的抗炎活性,是免疫应答的重要调节剂。IL-10直接影响APC通过下调MHC II类和共刺激分子在巨噬细胞和单核细胞表面的表达而起作用。IL-10抑制许多促炎细胞因子、趋化因子和趋化因子受体的表达,并介导过敏原特异性免疫治疗中的过敏原耐受性。IL-10抑制TH1淋巴细胞产生的IFN-g和IL-2,抑制TH2淋巴细胞产生IL-4和IL-5。IL-10还可以抑制细胞表面抗原的表达,如CD23、CD80、CD86等。

IL-10在疾病研究方面的应用比较广泛。比如在人类过敏性疾病中,IL-10起着重要的调节作用。有研究证明健康受试者的呼吸道中IL-10表达量比哮喘和过敏性鼻炎患者的呼吸道中含量高。在小鼠敲除IL-10实验中,可以生成慢性结肠炎。IL-10对嗜酸性粒细胞存活和IL-4诱导的IgE合成具有抑制作用。IL-10属于细胞毒性T细胞的生长辅助因子。细胞免疫和过敏性炎症相关的细胞因子的表达会被IL-10抑制。白介素IL-10还可以刺激体液应答。

IL-10通路的信号受损与炎症性肠病(IBD)等炎症性疾病有关,感染时常伴有免疫病理改变;相反,IL-10的高表达或失调可能导致慢性感染;另一方面,在某些情况下,IL-10具有免疫刺激功能,例如肥大细胞、B细胞和T细胞。

在肿瘤免疫治疗过程中,细胞因子作为一种免疫调节剂,直接刺激肿瘤部位的免疫效应细胞和基质细胞,可以用于激活免疫疗法、抑制免疫疗法等,增强细胞毒性,具有广泛的抗肿瘤活性。获得FDA批准上市的细胞因子药物已有多个,如高剂量的IL-2用于治疗黑素瘤和肾细胞癌,IFN-α用于III期黑素瘤的辅助治疗。还有更多的细胞因子已经进入临床试验阶段,如GM-CSF、IL-7、IL-12、IL-15、IL-18和IL-2。

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    2021-07-04 医鸣惊人

    认真学习了

    0

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CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1617933, encodeId=a5b8161e93301, content=<a href='/topic/show?id=e88f6930185' target=_blank style='color:#2F92EE;'>#生物学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69301, encryptionId=e88f6930185, topicName=生物学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e44019811593, createdName=12498c32m74暂无昵称, createdTime=Sun Jul 04 01:30:17 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=995711, encodeId=f253995e110c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210511/e9408422a23545ef9738dd674abfc4ff/c719925083844b82986bc39d43051172.jpg, 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    2021-07-04 axin009
  4. 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CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1617933, encodeId=a5b8161e93301, content=<a href='/topic/show?id=e88f6930185' target=_blank style='color:#2F92EE;'>#生物学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69301, encryptionId=e88f6930185, topicName=生物学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e44019811593, createdName=12498c32m74暂无昵称, createdTime=Sun Jul 04 01:30:17 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=995711, encodeId=f253995e110c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210511/e9408422a23545ef9738dd674abfc4ff/c719925083844b82986bc39d43051172.jpg, createdBy=8eb14795142, createdName=与狼共舞, createdTime=Sat Jul 03 14:05:46 CST 2021, time=2021-07-03, status=1, ipAttribution=)]
    2021-07-04 mashirong
  5. 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CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1617933, encodeId=a5b8161e93301, content=<a href='/topic/show?id=e88f6930185' target=_blank style='color:#2F92EE;'>#生物学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69301, encryptionId=e88f6930185, topicName=生物学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e44019811593, createdName=12498c32m74暂无昵称, createdTime=Sun Jul 04 01:30:17 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=995711, encodeId=f253995e110c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210511/e9408422a23545ef9738dd674abfc4ff/c719925083844b82986bc39d43051172.jpg, 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    2021-07-04 neurosurgeon
  6. 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CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1617933, encodeId=a5b8161e93301, content=<a href='/topic/show?id=e88f6930185' target=_blank style='color:#2F92EE;'>#生物学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69301, encryptionId=e88f6930185, topicName=生物学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e44019811593, createdName=12498c32m74暂无昵称, createdTime=Sun Jul 04 01:30:17 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=995711, encodeId=f253995e110c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210511/e9408422a23545ef9738dd674abfc4ff/c719925083844b82986bc39d43051172.jpg, createdBy=8eb14795142, createdName=与狼共舞, createdTime=Sat Jul 03 14:05:46 CST 2021, time=2021-07-03, status=1, ipAttribution=)]
    2021-07-04 jjjiang0202

    #IL-1#

    0

  7. 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CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1617933, encodeId=a5b8161e93301, content=<a href='/topic/show?id=e88f6930185' target=_blank style='color:#2F92EE;'>#生物学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69301, encryptionId=e88f6930185, topicName=生物学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e44019811593, createdName=12498c32m74暂无昵称, createdTime=Sun Jul 04 01:30:17 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=995711, encodeId=f253995e110c, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210511/e9408422a23545ef9738dd674abfc4ff/c719925083844b82986bc39d43051172.jpg, createdBy=8eb14795142, createdName=与狼共舞, createdTime=Sat Jul 03 14:05:46 CST 2021, time=2021-07-03, status=1, ipAttribution=)]
    2021-07-04 柳叶一刀

    #IL-10#

    0

  8. 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    2021-07-03 与狼共舞

    学习

    0