Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics.
Lymph node homeostasis and adaptation to immune challenge resolved by fibroblast network mechanics.
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DOI：
10.1038/s41590-022-01272-5
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发表时间：
2022-08
影响因子：
30.5
通讯作者：
Acton, Sophie E.
中科院分区：
文献类型：
--
作者：
Horsnell, Harry L.;Tetley, Robert J.;De Belly, Henry;Makris, Spyridon;Millward, Lindsey J.;Benjamin, Agnesska C.;Heeringa, Lucas A.;de Winde, Charlotte M.;Paluch, Ewa K.;Mao, Yanlan;Acton, Sophie E.
组织的自然物理性质不容易通过对其组成细胞的还原论研究来理解。在这里，我们显示控制细胞，物理和结构特性的分子信号，并共同确定淋巴结，免疫相关的成人组织的组织力学。淋巴结矛盾地保持稳健的组织结构在稳态，但不断准备广泛的扩展后，免疫挑战。我们发现，在免疫挑战的小鼠模型中，成纤维细胞的细胞网络的细胞骨架力学决定组织张力独立的细胞外基质支架。我们确定C型凝集素样受体2（CLEC-2）-podoplanin信号调节成纤维细胞的细胞表面力学，提供了一个机械敏感的途径来调节淋巴结重塑。通过podoplanin基因缺失干扰成纤维细胞力学减弱T细胞活化。我们发现，通过成纤维细胞间质网增加的组织张力是触发成纤维细胞增殖的启动和通过淋巴结扩张恢复稳态细胞比例和组织结构所必需的。阿克顿和他的同事们研究了免疫反应过程中淋巴结肿胀的机制。他们发现组织张力调节淋巴结扩张期间成纤维网状细胞（FRC）的增殖，并且FRC中的podoplanin（PDPN）-CLEC-2信号传导调节这一过程，进而调节T细胞活化。
Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular, physical, and structural properties and collectively determine tissue mechanics of lymph nodes, an immunologically relevant adult tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive expansion upon immune challenge. We find that in murine models of immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that C-type lectin-like receptor 2 (CLEC-2)–podoplanin signaling regulates the cell surface mechanics of fibroblasts, providing a mechanically sensitive pathway to regulate lymph node remodeling. Perturbation of fibroblast mechanics through genetic deletion of podoplanin attenuates T cell activation. We find that increased tissue tension through the fibroblastic stromal meshwork is required to trigger the initiation of fibroblast proliferation and restore homeostatic cellular ratios and tissue structure through lymph node expansion. Acton and colleagues examine the mechanics of lymph node swelling during the course of an immune response. They find tissue tension regulates fibroblastic reticular cell (FRC) proliferation during lymph node expansion and that podoplanin (PDPN)–CLEC-2 signaling in FRCs regulates this process, which in turn regulates T cell activation.
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淋巴细胞昼夜节律的时钟控制淋巴结运输和适应性免疫反应。
影响因子：
32.4
作者：
Druzd D;Matveeva O;Ince L;Harrison U;He W;Schmal C;Herzel H;Tsang AH;Kawakami N;Leliavski A;Uhl O;Yao L;Sander LE;Chen CS;Kraus K;de Juan A;Hergenhan SM;Ehlers M;Koletzko B;Haas R;Solbach W;Oster H;Scheiermann C
通讯作者：
Scheiermann C
影响因子：
23.9
作者：
De Belly H;Stubb A;Yanagida A;Labouesse C;Jones PH;Paluch EK;Chalut KJ
通讯作者：
Chalut KJ
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
--
作者：
Belanger，Maura C.;Ball，Alexander G.;Pompano，Rebecca R.
通讯作者：
Pompano，Rebecca R.
影响因子：
9.2
作者：
Farhadifar, Reza;Roeper, Jens-Christian;Juelicher, Frank
通讯作者：
Juelicher, Frank