Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines.
Epithelial Cell-Associated Galectin-3 Activates Human Dendritic Cell Subtypes for Pro-Inflammatory Cytokines.
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DOI：
10.3389/fimmu.2020.524826
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发表时间：
2020
影响因子：
7.3
通讯作者：
Bieneman AP
中科院分区：
文献类型：
--
作者：
Schroeder JT;Adeosun AA;Bieneman AP
越来越多的证据表明，半乳糖凝集素-3是与多种疾病和病症相关的预后和诊断生物标志物，包括癌症、心血管疾病、自身免疫、伤口愈合、过敏性疾病和一般的慢性炎症。然而，半乳糖凝集素-3是否以及如何参与这些疾病的发病机制仍然知之甚少。最近，我们已经将半乳糖凝集素-3在A549上皮细胞系（腺癌）上的表达与人嗜碱性粒细胞的激活联系起来，以释放组胺和分泌IL-4和IL-13。这些反应被证明依赖于细胞与细胞的接触，嗜碱性粒细胞表达的IgE，抑制N-乙酰乳糖胺，并消融时，嗜碱性粒细胞与A549克隆缺乏半乳糖凝集素-3的表达共培养。虽然重组半乳糖凝集素-3在溶液中不能激活嗜碱性粒细胞，但表达这种凝集素的微球通过模拟使用A549细胞时观察到的反应来激活嗜碱性粒细胞。考虑到嗜碱性粒细胞反应的IgE依赖性，以及长期以来已知半乳糖凝集素-3结合这种免疫球蛋白的事实，我们假设类似的激活模式延伸到其他携带IgE的细胞。为了研究这种可能性，我们测试了上皮细胞相关的半乳糖凝集素-3激活人树突状细胞的能力，包括浆细胞样和髓样亚型以及单核细胞，所有这些都结合IgE。事实上，结果表明，上皮细胞相关的半乳糖凝集素-3激活这些细胞，以稳健地产生TNF-α和IL-6，并上调树突状细胞上发现的激活标志物的表达。此外，许多先前观察到的嗜碱性粒细胞的相同参数适用于本文的发现，包括基质结合的半乳糖凝集素-3（无论是在上皮细胞上还是在微球上）促进这种激活模式的证据。与此相反，IgE的表达是这些半乳糖凝集素-3依赖性细胞因子的反应，这意味着这种凝集素激活树突状细胞（和单核细胞）的结合，而不是这种免疫球蛋白的糖蛋白。总的来说，这些发现进一步证明了半乳糖凝集素-3如何介导免疫细胞活化，为这种凝集素如何促进许多疾病发病机制的慢性炎症提供了新的见解。
There is mounting evidence that galectin-3 is a prognostic and diagnostic biomarker associated with diverse diseases and conditions, including cancer, cardiovascular disease, autoimmunity, wound healing, allergic disease, and chronic inflammation in general. Yet, whether and exactly how galectin-3 may participate in the pathogenesis of these diseases remains poorly understood. Recently, we have linked the expression of galectin-3 on the A549 epithelial cell line –an adenocarcinoma, to the activation of human basophils for the release of histamine and secretion of IL-4 and IL-13. These responses proved dependent on cell-to-cell contact, basophil expression of IgE, were inhibited by n-acetyllactosamine, and were ablated when basophils were co-cultured with A549 clones lacking galectin-3 expression. While recombinant galectin-3 failed to activate basophils when in solution, microspheres expressing this lectin did so by mimicking the responses seen when using A549 cells. Given the IgE dependency of the basophil responses, and the fact that galectin-3 is long known to bind this immunoglobulin, we hypothesize that a similar mode of activation extends to other IgE-bearing cells. To investigate this possibility, we tested epithelial cell-associated galectin-3 for its capacity to activate human dendritic cells, including the plasmacytoid and myeloid subtypes as well as monocytes, all of which bind IgE. Indeed, results indicate that epithelial cell-associated galectin-3 activated these cells for robust production of TNF-α and IL-6 and up-regulated the expression of activation markers found on dendritic cells. Moreover, many of the same parameters previously observed for basophils applied to the findings herein, including evidence that matrix-bound galectin-3 (whether on epithelial cells or microspheres) facilitates this mode of activation. In contrast, IgE expression was dispensable for these galectin-3-dependent cytokine responses, implying that this lectin activates dendritic cells (and monocytes) by binding to a glycoprotein other than this immunoglobulin. Overall, these findings further demonstrate how galectin-3 mediates immune cell activation, providing novel insight into how this lectin may promote chronic inflammation underlying the pathogenesis of many diseases.
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影响因子：
4.8
作者：
Niki, Toshiro;Tsutsui, Shoko;Hirashima, Mitsuomi
通讯作者：
Hirashima, Mitsuomi
影响因子：
4.4
作者：
Schroeder, JT;Bieneman, AP;Liu, MC
通讯作者：
Liu, MC
急性缺血性中风患者的血清半乳糖凝集素 3 与不良预后
影响因子：
8.3
作者：
Wang, Aili;Zhong, Chongke;He, Jiang
通讯作者：
He, Jiang
DOI：
10.4049/jimmunol.1700055
发表时间：
2017-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Schroeder JT;Bieneman AP
通讯作者：
Bieneman AP
DOI：
10.1016/j.jaci.2016.11.035
发表时间：
2017-07
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Rowe RK;Pyle DM;Tomlinson AR;Lv T;Hu Z;Gill MA
通讯作者：
Gill MA