Efficient T Cell Migration and Activation Require L-Plastin

Joshi, Hemant; Morley, Sharon Celeste

doi:10.3389/fimmu.2022.916137

Cited by 7 publications

(6 citation statements)

References 80 publications

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“…ITGAL is an important molecule in the interaction between leukocytes and other cells (e.g., endothelial cells), and its main function is to participate in cell adhesion and migration, which are important for cellular immune responses, inflammatory responses, etc. (8)(9)(10). Recent studies have discovered that ITGAL is enriched in the tumor microenvironment, drawing much interest in oncology (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates

Zhang,

Zhu,

et al. 2024

Front. Immunol.

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BackgroundIntegrin subunit alpha L (ITGAL) encodes an integrin component of LFA-1 and is a membrane receptor molecule widely expressed on leukocytes. It plays a key role in the interaction between white blood cells and other cells. There was a significant correlation between the expression of ITGAL and the tumor microenvironment in a number of cancers. However, experimental studies targeting ITGAL and immune cell infiltration in non-small-cell lung cancer (NSCLC) and the response to immune checkpoint inhibitor therapy are lacking.MethodsData were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases to explore the relationship between ITGAL expression and prognosis, as well as the immune cell infiltration in patients with NSCLC. In addition, immunohistochemical staining for ITGAL and multiplex immunofluorescence (mIF) staining for ITGAL, CD20, CD68, CD4, and CD8 from tissue microarrays containing 118 tumor tissues and paired paracancerous tissues from patients with NSCLC were performed. The correlation between ITGAL expression and clinical factors, as well as the immunophenotypes of tumor-infiltrating immune cells, were also analyzed.ResultsIn NSCLC tumor tissues, ITGAL was downregulated compared with matched paracancerous tissues, and low ITGAL expression was associated with a poor prognosis of NSCLC patients. Subsequently, immunohistochemistry results for tissue microarray showed that ITGAL expression was mainly elevated in tumor stroma and areas with highly infiltrated immune cells. ITGAL expression was higher in paracancerous tissues than tumor tissues. Furthermore, mIF results indicated that the patients with ITGAL-high expression tend had significantly higher CD8+ T cells, CD68+ macrophages, CD4+ T cells, and CD20+ B cells infiltration in their tumor tissues. Immunophenotypes were classified into three categories, that is deserted, excluded, and inflamed types, according to each kind of immune cell distribution in or around the cancer cell nest. MIF results showed that ITGAL expression level was correlated with the immunophenotypes. Furthermore, ITGAL expression was associated with the prognosis of NSCLC in patients with immune checkpoint inhibitor therapy and the patients with high ITGAL expression tends have better outcomes.ConclusionsITGAL may be used as a biomarker for assessing the immune microenvironment in patients with NSCLC.

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Section: Introductionmentioning

confidence: 99%

ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates

Zhang,

Zhu,

et al. 2024

Front. Immunol.

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“…Therefore, ICAM‐1 becomes a potential therapeutic target in PAH, and monitoring ICAM‐1 levels might be useful in looking for the development of PAH. The combination of integrin alpha L chain (ITGAL) and beta 2 chain (ITGB2) forms the lymphocyte function‐associated antigen‐1 (LFA‐1), which plays a critical role in the extravasation of immune cells from the bloodstream to the local tissues 47 . Through inside‐out signaling, chemokine signals induce a conformational change in LFA‐1 converting LFA‐1 to a moderate‐affinity state, which can promote cell adhesion to endothelial cells by the means of binding to ICAM‐1 48 .…”

Section: Discussionmentioning

confidence: 99%

“…The combination of integrin alpha L chain (ITGAL) and beta 2 chain (ITGB2) forms the lymphocyte function‐associated antigen‐1 (LFA‐1), which plays a critical role in the extravasation of immune cells from the bloodstream to the local tissues. 47 Through inside‐out signaling, chemokine signals induce a conformational change in LFA‐1 converting LFA‐1 to a moderate‐affinity state, which can promote cell adhesion to endothelial cells by the means of binding to ICAM‐1. 48 Thus, we speculated that blockage of the interaction between LFA‐1 and ICAM‐1 might relieve the development of PAH.…”

Section: Discussionmentioning

confidence: 99%

Identification of monocyte‐associated pathways participated in the pathogenesis of pulmonary arterial hypertension based on omics‐data

Zhong,

Si,

Yang

et al. 2023

Pulm. circ.

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Pulmonary arterial hypertension (PAH) is one kind of chronic and uncurable diseases that can cause heart failure. Immune microenvironment plays a significant role in PAH. The aim of this study was to assess the role of immune cell infiltration in the pathogenesis of PAH. Differentially expressed genes based on microarray data were enriched in several immune‐related pathways. To evaluate the immune cell infiltration, based on the microarray data sets in the GEO database, we used both ssGSEA and the CIBERSORT algorithm. Additionally, single‐cell RNA sequencing (scRNA‐seq) data was used to further explicit the specific role and intercellular communications. Then receiver operating characteristic curves and least absolute shrinkage and selection operator were used to discover and test the potential diagnostic biomarkers for PAH. Both the immune cell infiltration analyses based on the microarray data sets and the cell proportion in scRNA‐seq data exhibited a significant downregulation in the infiltration of monocytes in PAH. Then, the intercellular communications showed that the interaction weighs of most immune cells, including monocytes changed between the control and PAH groups, and the ITGAL‐ITGB2 and ICAM signaling pathways played critical roles in this process. In addition, ITGAM and ICAM2 displayed good diagnosis values in PAH. This study implicated that the change of monocyte was one of the key immunologic features of PAH. Monocyte‐associated ICAM‐1 and ITGAL‐ITGB2 signaling pathways might be involved in the pathogenesis of PAH.

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“…L-plastin supports the migration and invasive ability of various blood cells and contributes to the stability of the T-cell immune synapse and macrophage podosomes. It promotes platelet formation in a miR-125a-5p-dependent manner and enhances NLRP3 inflammasome assembly [ 149 , 150 , 151 , 152 , 153 ]. This isoform is linked to non-Hodgkin lymphoma [ 154 ], whereas its ectopic expression is associated with a high invasiveness in solid tumors [ 144 , 155 ].…”

Section: Actin-bundling Proteinsmentioning

confidence: 99%

Actin Bundles Dynamics and Architecture

2023

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Cells use the actin cytoskeleton for many of their functions, including their division, adhesion, mechanosensing, endo- and phagocytosis, migration, and invasion. Actin bundles are the main constituent of actin-rich structures involved in these processes. An ever-increasing number of proteins that crosslink actin into bundles or regulate their morphology is being identified in cells. With recent advances in high-resolution microscopy and imaging techniques, the complex process of bundles formation and the multiple forms of physiological bundles are beginning to be better understood. Here, we review the physiochemical and biological properties of four families of highly conserved and abundant actin-bundling proteins, namely, α-actinin, fimbrin/plastin, fascin, and espin. We describe the similarities and differences between these proteins, their role in the formation of physiological actin bundles, and their properties—both related and unrelated to their bundling abilities. We also review some aspects of the general mechanism of actin bundles formation, which are known from the available information on the activity of the key actin partners involved in this process.

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Efficient T Cell Migration and Activation Require L-Plastin

Cited by 7 publications

References 80 publications

ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates

ITGAL expression in non-small-cell lung cancer tissue and its association with immune infiltrates

Identification of monocyte‐associated pathways participated in the pathogenesis of pulmonary arterial hypertension based on omics‐data

Actin Bundles Dynamics and Architecture

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