LFA-1 在 T 细胞迁移和分化中的作用。

LFA-1 in T Cell Migration and Differentiation.

机构信息

Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY, United States.

出版信息

Front Immunol. 2018 May 3;9:952. doi: 10.3389/fimmu.2018.00952. eCollection 2018.

Abstract

Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration. With 24 integrin pairs having been discovered to date, integrins are defined not only by the composition of the heterodimeric pair but by cell-type specific expression and their ligands. Furthermore, integrins not only facilitate adhesion but also induce intracellular signaling and have recently been uncovered as mechanosensors providing additional complexity to the signaling pathways. Among several leukocyte-specific integrins, lymphocyte function-associated antigen-1 (LFA-1 or αβ; CD11a/CD18) is a key T cell integrin, which plays a major role in regulating T cell activation and migration. Adhesion to LFA-1's ligand, intracellular adhesion receptor 1 (ICAM-1) facilitates firm endothelium adhesion, prolonged contact with antigen-presenting cells, and binding to target cells for killing. While the downstream signaling pathways utilized by LFA-1 are vastly conserved they allow for highly disparate responses. Here, we summarize the roles of LFA-1 and ongoing studies to better understand its functions and regulation.

摘要

维持体内免疫监视的稳态和产生有效的适应性免疫应答,需要精细调控淋巴细胞在体内的时空迁移,以确保病原体的清除和记忆的产生。淋巴细胞的激活和迁移失调可导致适应性免疫受损、反复感染以及一系列自身免疫性疾病和慢性炎症。整合素作为细胞表面受体,在招募 T 细胞中起核心作用,其调节细胞黏附、信号转导和迁移。迄今为止,已发现 24 对整合素对,整合素不仅由异二聚体对的组成定义,还由细胞类型特异性表达及其配体定义。此外,整合素不仅促进黏附,还诱导细胞内信号转导,最近还被发现作为机械感受器,为信号通路提供了额外的复杂性。在几种白细胞特异性整合素中,淋巴细胞功能相关抗原-1(LFA-1 或 αβ;CD11a/CD18)是一种关键的 T 细胞整合素,在调节 T 细胞激活和迁移中发挥重要作用。与 LFA-1 的配体细胞间黏附分子 1(ICAM-1)的黏附有助于 T 细胞与内皮细胞牢固黏附、与抗原呈递细胞长时间接触,并与靶细胞结合进行杀伤。虽然 LFA-1 利用的下游信号通路具有广泛的保守性,但它们允许产生高度不同的反应。在此,我们总结了 LFA-1 的作用及正在进行的研究,以更好地理解其功能和调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1293/5943560/ba562d2c58fc/fimmu-09-00952-g001.jpg

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