ICAMs in Immunity, Intercellular Adhesion and Communication

Abstract

Interactions among leukocytes and leukocytes with immune-associated auxiliary cells represent an essential feature of the immune response that requires the involvement of cell adhesion molecules (CAMs). In the immune system, CAMs include a wide range of members pertaining to different structural and functional families involved in cell development, activation, differentiation and migration. Among them, β2 integrins (LFA-1, Mac-1, p150,95 and αDβ2) are predominantly involved in homotypic and heterotypic leukocyte adhesion. β2 integrins bind to intercellular (I)CAMs, actin cytoskeleton-linked receptors belonging to immunoglobulin superfamily (IgSF)-CAMs expressed by leukocytes and vascular endothelial cells, enabling leukocyte activation and transendothelial migration. β2 integrins have long been viewed as the most important ICAMs partners, propagating intracellular signalling from β2 integrin-ICAM adhesion receptor interaction. In this review, we present previous evidence from pioneering studies and more recent findings supporting an important role for ICAMs in signal transduction. We also discuss the contribution of immune ICAMs (ICAM-1, -2, and -3) to reciprocal cell signalling and function in processes in which β2 integrins supposedly take the lead, paying particular attention to T cell activation, differentiation and migration.

Identification of crucial inflammaging related risk factors in multiple sclerosis

“…The top ten KEGG pathways were shown in Table 5 (Lasky, 1991 ; Reichardt, 2006 ; Fujita et al, 2009 ; O'Callaghan et al, 2017 ; Conway, 2018 ; Gao et al, 2018 ; Kotelnikova et al, 2019 ; Plantone et al, 2019 ; Ten Bosch et al, 2021 ; Bahadoram et al, 2022 ; Bohmwald et al, 2022 ; Sen et al, 2022 ; Wu and Zhou, 2022 ; Chen et al, 2023 ; Liu et al, 2023 ; Touil et al, 2023 ; Guerra-Espinosa et al, 2024 ) and Figure 3 and Supplementary Figure S1 (without the starting point). For example, the KEGG pathway that was most enriched shortest paths was “B CELL RECEPTOR SIGNALING PATHWAY” (enriched 50 shortest paths, Figure 3A and Supplementary Figure S1A ).…”

“…The top ten KEGG pathways were shown in Supplementary Table S5 (containing the starting point) (Lasky, 1991 ; Reichardt, 2006 ; Allen et al, 2007 ; O'Callaghan et al, 2017 ; Conway, 2018 ; Gao et al, 2018 ; Kotelnikova et al, 2019 ; Plantone et al, 2019 ; Cui et al, 2020 ; Amoriello et al, 2021 ; Balkan and Bilge, 2021 ; Wu and Zhou, 2022 ; Chen et al, 2023 ; Leonard and Lin, 2023 ; Suptela and Marriott, 2023 ; Touil et al, 2023 ; Guerra-Espinosa et al, 2024 ). For example, one enriched pathway was “COMPLEMENT AND COAGULATION CASCADES,” where complement and coagulation were major blood-borne proteolytic cascades (Conway, 2018 ).…”

“…To further explore potential underlying mechanisms between inflammaging and MS, each shortest path between inflammatory and disease markers was obtained based on the Dijkstra algorithm, then the enrichment analysis was performed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Biological Process (BP) terms in Gene Ontology (GO). Because the (Lasky, 1991;Reichardt, 2006;Fujita et al, 2009;O'Callaghan et al, 2017;Conway, 2018;Gao et al, 2018;Kotelnikova et al, 2019;Plantone et al, 2019;Ten Bosch et al, 2021;Bahadoram et al, 2022;Bohmwald et al, 2022;Sen et al, 2022;Wu and Zhou, 2022;Touil et al, 2023;Guerra-Espinosa et al, 2024) and Figure 3 and Supplementary Figure S1 (without the starting point). For example, the KEGG pathway that was most enriched shortest paths was "B CELL RECEPTOR SIGNALING PATHWAY" (enriched 50 shortest paths, Figure 3A and Supplementary Figure S1A).…”

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression

“…Moreover, among the top transcripts (from the first and second components) discriminating the 3 age groups, there were genes implicated in key signaling pathways that regulate aging and promote lifespan, many of which have been implicated in cellular senescence. For example, the ICAM4 is a gene that encodes a protein involved in cell–cell adhesion, which is critical for the immune system's proper function, allowing immune cells to migrate, attach and detach from other cells during an immune response and inflammation [ 38 ]. Dysregulation of ICAM genes can lead to chronic inflammation and immune dysfunction, which are common features of aging and many chronic diseases.…”

Molecular Determinants Involved in the Docking and Uptake of Tumor-Derived Extracellular Vesicles: Implications in Cancer

“…Structurally, ICAM-1 is a type-I transmembrane protein that belongs to the immunoglobulin protein superfamily (IgSF), and comprises five extracellular immunoglobulin domains (D1–D5), one transmembrane domain, and a short cytoplasmic tail that links this molecule with the actin cytoskeleton [ 54 , 56 ]. ICAM-1/CD54 is constitutively expressed at relatively low levels on the endothelium, leukocytes, and many other cell types (including cancer cells), but its expression is dramatically increased by multiple inflammatory stimuli, including TNFα, IFN-γ, and IL-1 (reviewed in [ 57 , 58 , 59 , 60 ]). ICAM-1/CD54 is recognized primarily by integrin αLβ2 (also known as CD11a/CD18 or LFA-1 “Leukocyte Function-associated Antigen-1”) but is also known to be a ligand of integrin αMβ2 (CD11b/CD18 or Mac-1) and probably also of αXβ2 (CD11c/CD18 or gp150-95) [ 57 , 61 , 62 ], although in the latter case, it is not clear whether binding of ICAM-1 to integrin αXβ2 takes place directly or through fibrinogen, which would act as a bridge molecule between them [ 57 ].…”