Advances in Leukocyte Migration and Location in Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 5041

Special Issue Editors

Research Assistant Professor, Department of Microbiology and Immunology, Center for Vaccine Biology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
Interests: innate immunology; immunity to infectious diseases; cell migration; immunobiology of signal transduction; lung mucosal immunity; immunometabolism

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Guest Editor
Children’s Mercy Research Institute, Kansas City, MO, USA
Interests: stem cells; immunotherapy; cancer stem cells; therapy resistance; drug discovery; pediatric cancer
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Special Issue Information

Dear Colleagues,

Immune cells are a critical component of the body that is responsible for fighting infection and disease. This diverse cell population develops, differentiates, matures, and is disposed of in the bone marrow and circulatory system. Often loaded with cytotoxic reagents that could destroy host tissue, immune cells are generally isolated in circulation from peripheral tissues within a healthy body. Because of this isolation and the characteristic patrolling nature of immune cells, they exhibit an incredible capacity for mobility to efficiently and specifically respond to pathogens and tissue damage. Importantly, immune cells are autonomous migrators, reliant on integrins and other molecules readily expressed on the cell surface, and thus their trafficking activities are tightly regulated by extracellular cues, which are largely provided by cells residing at barriers. The production and release of migration-inducing cues are dependent on the detection of non-self and self components that should be confined within cells. A massive immune cell infiltration, which usually occurs in response to barrier breaches, culminates in an often irreversible tissue remodeling and reconstitution of tissue immune components. In a healthy system, some kinds of immune cells enter the parenchyma of tissues slowly and steadily, becoming sentinels and replacing old tissue-resident immune cells, which is an important process to maintain tissue homeostasis.

While remarkable advances have been made during the past several decades, there are several outstanding questions regarding the physiological and pathological migration and location of leukocytes in health and disease: understanding of the spatial regulation of immune cell migration in the context of tissue structures, how a single immune cell integrates and responds to an array of various signals, or how a bulk of immune cells migrate to their target collectively. Further, the precise physio-mechanical mechanisms underlying immune cell locomotion are yet to be understood, with opportunities to understand metabolic pathways that regulate cell migration. Finally, mechanisms that govern infection vulnerability in elderly people and people with chronic diseases may be causally related to immune cell migration. Investigating these outstanding questions can lead to the development of efficacious therapeutic methods that manipulate immune cell migration to cure diseases. We collegially invite you to our forum for discussion to understand leukocyte migration and location and to implement the knowledge to improve human health. 

Dr. Kihong Lim
Dr. John M. Perry
Guest Editors

Manuscript Submission Information

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Published Papers (4 papers)

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Research

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14 pages, 3276 KiB  
Article
Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling
by Jing Wu, Maximilian Bley, Russell S. Steans, Allison M. Meadows, Rebecca D. Huffstutler, Rong Tian, Julian L. Griffin and Michael N. Sack
Cells 2024, 13(5), 455; https://doi.org/10.3390/cells13050455 - 5 Mar 2024
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Abstract
NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell [...] Read more.
NAD+ boosting via nicotinamide riboside (NR) confers anti-inflammatory effects. However, its underlying mechanisms and therapeutic potential remain incompletely defined. Here, we showed that NR increased the expression of CC-chemokine receptor 7 (CCR7) in human M1 macrophages by flow cytometric analysis of cell surface receptors. Consequently, chemokine ligand 19 (CCL19, ligand for CCR7)-induced macrophage migration was enhanced following NR administration. Metabolomics analysis revealed that prostaglandin E2 (PGE2) was increased by NR in human monocytes and in human serum following in vivo NR supplementation. Furthermore, NR-mediated upregulation of macrophage migration through CCL19/CCR7 was dependent on PGE2 synthesis. We also demonstrated that NR upregulated PGE2 synthesis through SIRT3-dependent post-transcriptional regulation of cyclooxygenase 2 (COX-2). The NR/SIRT3/migration axis was further validated using the scratch-test model where NR and SIRT3 promoted more robust migration across a uniformly disrupted macrophage monolayer. Thus, NR-mediated metabolic regulation of macrophage migration and wound healing may have therapeutic potential for the topical management of chronic wound healing. Full article
(This article belongs to the Special Issue Advances in Leukocyte Migration and Location in Health and Disease)
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15 pages, 1993 KiB  
Article
Sex-Based Disparities in Leukocyte Migration and Activation in Response to Inhalation Lung Injury: Role of SDF-1/CXCR4 Signaling
by Tanima Chatterjee, Terry L. Lewis, Itika Arora, Anastasiia E. Gryshyna, Lilly Underwood, Juan Xavier Masjoan Juncos and Saurabh Aggarwal
Cells 2023, 12(13), 1719; https://doi.org/10.3390/cells12131719 - 26 Jun 2023
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Abstract
The aim of the study was to determine whether sex-related differences exist in immune response to inhalation lung injury. C57BL/6 mice were exposed to Cl2 gas (500 ppm for 15, 20, or 30 min). Results showed that male mice have higher rates [...] Read more.
The aim of the study was to determine whether sex-related differences exist in immune response to inhalation lung injury. C57BL/6 mice were exposed to Cl2 gas (500 ppm for 15, 20, or 30 min). Results showed that male mice have higher rates of mortality and lung injury than females. The binding of the chemokine ligand C-X-C motif chemokine 12 (CXCL12), also called stromal-derived-factor-1 (SDF-1), to the C-X-C chemokine receptor type 4 (CXCR4) on lung cells promotes the migration of leukocytes from circulation to lungs. Therefore, the hypothesis was that elevated SDF-1/CXCR4 signaling mediates exaggerated immune response in males. Plasma, blood leukocytes, and lung cells were collected from mice post-Cl2 exposure. Plasma levels of SDF-1 and peripheral levels of CXCR4 in lung cells were higher in male vs. female mice post-Cl2 exposure. Myeloperoxidase (MPO) and elastase activity was significantly increased in leukocytes of male mice exposed to Cl2. Lung cells were then ex vivo treated with SDF-1 (100 ng/mL) in the presence or absence of the CXCR4 inhibitor, AMD3100 (100 nM). SDF-1 significantly increased migration, MPO, and elastase activity in cells obtained from male vs. female mice post-Cl2 exposure. AMD3100 attenuated these effects, suggesting that differential SDF-1/CXCR4 signaling may be responsible for sex-based disparities in the immune response to inhalation lung injury. Full article
(This article belongs to the Special Issue Advances in Leukocyte Migration and Location in Health and Disease)
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Review

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55 pages, 3101 KiB  
Review
Immune Cell Migration to Cancer
by Allison T. Ryan, Minsoo Kim and Kihong Lim
Cells 2024, 13(10), 844; https://doi.org/10.3390/cells13100844 - 16 May 2024
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Abstract
Immune cell migration is required for the development of an effective and robust immune response. This elegant process is regulated by both cellular and environmental factors, with variables such as immune cell state, anatomical location, and disease state that govern differences in migration [...] Read more.
Immune cell migration is required for the development of an effective and robust immune response. This elegant process is regulated by both cellular and environmental factors, with variables such as immune cell state, anatomical location, and disease state that govern differences in migration patterns. In all cases, a major factor is the expression of cell surface receptors and their cognate ligands. Rapid adaptation to environmental conditions partly depends on intrinsic cellular immune factors that affect a cell’s ability to adjust to new environment. In this review, we discuss both myeloid and lymphoid cells and outline key determinants that govern immune cell migration, including molecules required for immune cell adhesion, modes of migration, chemotaxis, and specific chemokine signaling. Furthermore, we summarize tumor-specific elements that contribute to immune cell trafficking to cancer, while also exploring microenvironment factors that can alter these cellular dynamics within the tumor in both a pro and antitumor fashion. Specifically, we highlight the importance of the secretome in these later aspects. This review considers a myriad of factors that impact immune cell trajectory in cancer. We aim to highlight the immunotherapeutic targets that can be harnessed to achieve controlled immune trafficking to and within tumors. Full article
(This article belongs to the Special Issue Advances in Leukocyte Migration and Location in Health and Disease)
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23 pages, 1994 KiB  
Review
ICAMs in Immunity, Intercellular Adhesion and Communication
by Claudia Guerra-Espinosa, María Jiménez-Fernández, Francisco Sánchez-Madrid and Juan M. Serrador
Cells 2024, 13(4), 339; https://doi.org/10.3390/cells13040339 - 14 Feb 2024
Cited by 1 | Viewed by 1324
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Advances in Leukocyte Migration and Location in Health and Disease)
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