Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.
Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.
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DOI：
10.1038/s41590-023-01519-9
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发表时间：
2023-07
影响因子：
30.5
通讯作者：
Linterman, Michelle A.
中科院分区：
文献类型：
--
作者：
Silva-Cayetano, Alyssa;Fra-Bido, Sigrid;Robert, Philippe A.;Innocentin, Silvia;Burton, Alice R.;Watson, Emily M.;Lee, Jia Le;Webb, Louise M. C.;Foster, William S.;McKenzie, Ross C. J.;Bignon, Alexandre;Vanderleyden, Ine;Alterauge, Dominik;Lemos, Julia P.;Carr, Edward J.;Hill, Danika L.;Cinti, Isabella;Balabanian, Karl;Baumjohann, Dirk;Espeli, Marion;Meyer-Hermann, Michael;Denton, Alice E.;Linterman, Michelle A.
生发中心(GC)反应的大小和质量随着年龄的增长而下降，导致老年人的疫苗诱导免疫力较差。功能性GC需要跨越时间和空间的多种细胞类型的协调，特别是跨越两个功能不同的隔间：亮区和暗区。在老年小鼠中，CXCR4介导的T滤泡辅助细胞(TFH)错误定位到暗区，而滤泡树突状细胞(FDCs)在光区形成压缩网络。在这里，我们表明TFH细胞的定位对于抗体反应的质量和免疫后FDC网络的扩大至关重要。老年小鼠较小的GC和压缩的FDC网络通过提供TFH细胞来纠正，这些细胞使用CXCR5与FDC共存。这表明GC反应中与年龄相关的缺陷是可逆的，并表明TFH细胞支持基质细胞对疫苗的反应。林特曼和他的同事研究了老年人生发中心的形成。他们发现，衰老的TFH细胞具有CXCR4的异常表达，这导致这些细胞在生发中心的空间定位错误，削弱了它们为B细胞提供帮助和促进抗体产生的能力。
The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines. Linterman and colleagues examine germinal center formation in older individuals. They find that aged TFH cells have dysregulated CXCR4 expression, which causes spatial mislocalization of these cells in germinal centers, impairing their ability to provide help to B cells and to promote antibody production.
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影响因子：
5.4
作者：
Bradford BM;Reizis B;Mabbott NA
通讯作者：
Mabbott NA
DOI：
10.4049/jimmunol.0901296
发表时间：
2010-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jones SC;Brahmakshatriya V;Huston G;Dibble J;Swain SL
通讯作者：
Swain SL
影响因子：
4.6
作者：
Lefebvre JS;Masters AR;Hopkins JW;Haynes L
通讯作者：
Haynes L
影响因子：
32.4
作者：
Bannard O;Horton RM;Allen CD;An J;Nagasawa T;Cyster JG
通讯作者：
Cyster JG
影响因子：
5.4
作者：
Elsner, Rebecca A.;Ernst, David N.;Baumgarth, Nicole
通讯作者：
Baumgarth, Nicole