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通过半乳糖凝集素-聚糖相互作用塑造造血细胞生态系统。

Shaping hematopoietic cell ecosystems through galectin-glycan interactions.

作者信息

Schattner Mirta, Psaila Bethan, Rabinovich Gabriel A

机构信息

Laboratorio de Glicomedicina, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad de Buenos Aires 1428, Argentina; Laboratorio de Trombosis Experimental e Inmunobiología de la Inflamación, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Ciudad de Buenos Aires 1425, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires 1428, Argentina.

MRC Weatherall Institute of Molecular Medicine and Ludwig Institute for Cancer Research, University of Oxford, Oxford OX3 9DS, United Kingdom.

出版信息

Semin Immunol. 2024 Jul-Sep;74-75:101889. doi: 10.1016/j.smim.2024.101889. Epub 2024 Oct 14.

DOI:10.1016/j.smim.2024.101889
PMID:39405834
Abstract

Hematopoiesis- the formation of blood cell components- continually replenishes the blood system during embryonic development and postnatal lifespans. This coordinated process requires the synchronized action of a broad range of cell surface associated proteins and soluble mediators, including growth factors, cytokines and lectins. Collectively, these mediators control cellular communication, signalling, commitment, proliferation, survival and differentiation. Here we discuss the role of galectins - an evolutionarily conserved family of glycan-binding proteins - in the establishment and dynamic remodelling of hematopoietic niches. We focus on the contribution of galectins to B and T lymphocyte development and selection, as well as studies highlighting the role of these proteins in myelopoiesis, with particular emphasis on erythropoiesis and megakaryopoiesis. Finally, we also highlight recent findings suggesting the role of galectin-1, a prototype member of this protein family, as a key pathogenic factor and therapeutic target in myelofibrosis. Through extracellular or intracellular mechanisms, galectins can influence the fate and function of distinct hematopoietic progenitors and fine-tune the final repertoire of blood cells, with critical implications in a wide range of physiologically vital processes including innate and adaptive immunity, immune tolerance programs, tissue repair, regeneration, angiogenesis, inflammation, coagulation and oxygen delivery. Additionally, positive or negative regulation of galectin-driven circuits may contribute to a broad range of blood cell disorders.

摘要

造血作用——血细胞成分的形成——在胚胎发育和出生后的生命周期中持续补充血液系统。这个协调的过程需要多种细胞表面相关蛋白和可溶性介质的同步作用,包括生长因子、细胞因子和凝集素。总的来说,这些介质控制细胞间的通讯、信号传导、定向、增殖、存活和分化。在这里,我们讨论半乳糖凝集素——一类进化上保守的聚糖结合蛋白家族——在造血微环境的建立和动态重塑中的作用。我们重点关注半乳糖凝集素对B淋巴细胞和T淋巴细胞发育及选择的贡献,以及突出这些蛋白在髓系造血,特别是红细胞生成和巨核细胞生成中作用的研究。最后,我们还强调了最近的研究发现,即该蛋白家族的原型成员半乳糖凝集素-1在骨髓纤维化中作为关键致病因素和治疗靶点的作用。通过细胞外或细胞内机制,半乳糖凝集素可以影响不同造血祖细胞的命运和功能,并微调血细胞的最终组成,这对包括先天和适应性免疫、免疫耐受程序、组织修复、再生、血管生成、炎症、凝血和氧气输送在内的广泛生理重要过程具有关键意义。此外,对半乳糖凝集素驱动回路的正向或负向调节可能导致多种血细胞疾病。

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