Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation.
Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation.
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DOI：
10.1073/pnas.2023174118
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发表时间：
2021-09-07
影响因子：
11.1
通讯作者：
Meyer Zu Horste G
中科院分区：
文献类型：
--
作者：
Hartlehnert M;Börsch AL;Li X;Burmeister M;Gerwien H;Schafflick D;Heming M;Lu IN;Narayanan V;Strecker JK;Kolz A;Peters A;Wu GF;Wiendl H;Sorokin L;Meyer Zu Horste G
脑膜保护中枢神经系统，但也保护神经炎症中的宿主淋巴细胞。在人类多发性硬化症中，B细胞优先在脑膜中积聚。通过生成实验性神经炎症中脑膜与实质白细胞的隔室特异性转录图谱，我们发现脑膜B细胞的滤泡表型和脑膜Th 17细胞中相应的滤泡辅助细胞样表型。因此，脑膜指示位点特异性局部表型为促炎性自身反应性T细胞。我们鉴定了Th 17细胞中的转录因子Bcl 6促进与脑膜B细胞、同种型转换和B细胞支持趋化因子的相互作用。这可能描述了一种控制脑膜自身免疫的机制，并有助于理解脑膜作为最近认识到的免疫活性部位如何促进多发性硬化症中的自身免疫组织损伤。含有B细胞的异位淋巴组织在人类多发性硬化症（MS）的晚期以及当啮齿动物中产生白介素（IL）-17的T辅助（Th 17）细胞诱导神经炎症时在脑膜中形成。B细胞分化和随后的类别转换免疫球蛋白的释放被推测发生在脑膜中，但脑膜主导的炎症的确切细胞组成和潜在机制仍然未知。在这里，我们进行了深入的表征脑膜与实质Th 17诱导的啮齿动物神经炎症。这些隔室之间最显著的细胞和转录差异是B细胞的定位，其仅表现出脑膜的滤泡表型。相应地，脑膜而非实质Th 17细胞获得了支持B细胞的表型，并与B细胞紧密接触。这种优先B细胞对脑膜的嗜性和脑膜异位淋巴组织的形成部分依赖于转录因子Bcl 6在Th 17细胞中的表达，这是其他T细胞谱系诱导B细胞中同种型类别转换所必需的。Bcl 6在Th 17细胞中的功能仅在体内检测到，并通过B细胞支持细胞因子的诱导、脑膜中滤泡B细胞的出现和脑脊液中免疫球蛋白类别转换来反映。因此，我们确定了一个B细胞支持脑膜微环境的诱导Bcl 6在Th 17细胞作为一种机制，控制区室特异性神经炎症。
The meninges protect the central nervous system but also host lymphocytes in neuroinflammation. In human multiple sclerosis, preferentially B cells accumulate in the meninges. By generating a compartment-specific transcriptional map of meningeal versus parenchymal leukocytes in experimental neuroinflammation, we found a follicular phenotype of meningeal B cells and a corresponding follicular helper-like phenotype in meningeal Th17 cells. The meninges thus instructed a site-specific local phenotype to proinflammatory autoreactive T cells. We identified the transcription factor Bcl6 in Th17 cells to promote interactions with meningeal B cells, isotype-switching, and B cell-supporting chemokines. This may describe a mechanism controlling meningeal autoimmunity and helps understanding how the meninges, as a recently recognized immunologically active site, contribute to autoimmune tissue damage in multiple sclerosis. Ectopic lymphoid tissue containing B cells forms in the meninges at late stages of human multiple sclerosis (MS) and when neuroinflammation is induced by interleukin (IL)-17 producing T helper (Th17) cells in rodents. B cell differentiation and the subsequent release of class-switched immunoglobulins have been speculated to occur in the meninges, but the exact cellular composition and underlying mechanisms of meningeal-dominated inflammation remain unknown. Here, we performed in-depth characterization of meningeal versus parenchymal Th17-induced rodent neuroinflammation. The most pronounced cellular and transcriptional differences between these compartments was the localization of B cells exhibiting a follicular phenotype exclusively to the meninges. Correspondingly, meningeal but not parenchymal Th17 cells acquired a B cell–supporting phenotype and resided in close contact with B cells. This preferential B cell tropism for the meninges and the formation of meningeal ectopic lymphoid tissue was partially dependent on the expression of the transcription factor Bcl6 in Th17 cells that is required in other T cell lineages to induce isotype class switching in B cells. A function of Bcl6 in Th17 cells was only detected in vivo and was reflected by the induction of B cell–supporting cytokines, the appearance of follicular B cells in the meninges, and of immunoglobulin class switching in the cerebrospinal fluid. We thus identify the induction of a B cell–supporting meningeal microenvironment by Bcl6 in Th17 cells as a mechanism controlling compartment specificity in neuroinflammation.
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DOI：
10.1084/jem.20141380
发表时间：
2015-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hatzi K;Nance JP;Kroenke MA;Bothwell M;Haddad EK;Melnick A;Crotty S
通讯作者：
Crotty S
影响因子：
7.3
作者：
Dang AK;Tesfagiorgis Y;Jain RW;Craig HC;Kerfoot SM
通讯作者：
Kerfoot SM
全基因组分析确定了T卵泡辅助细胞分化过程中Bcl6控制的调节网络。
影响因子：
8.8
作者：
Liu X;Lu H;Chen T;Nallaparaju KC;Yan X;Tanaka S;Ichiyama K;Zhang X;Zhang L;Wen X;Tian Q;Bian XW;Jin W;Wei L;Dong C
通讯作者：
Dong C
影响因子：
64.5
作者：
Gaublomme JT;Yosef N;Lee Y;Gertner RS;Yang LV;Wu C;Pandolfi PP;Mak T;Satija R;Shalek AK;Kuchroo VK;Park H;Regev A
通讯作者：
Regev A
DOI：
10.4049/jimmunol.1300378
发表时间：
2013-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hollister K;Kusam S;Wu H;Clegg N;Mondal A;Sawant DV;Dent AL
通讯作者：
Dent AL