Tuning immunity through tissue mechanotransduction

Du, Huixun; Bartleson, Juliet M.; Butenko, Sergei; Alonso, Valentina; Liu, Wendy F.; Winer, Daniel A.; Butte, Manish J.

doi:10.1038/s41577-022-00761-w

Cited by 124 publications

(109 citation statements)

References 195 publications

(256 reference statements)

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“…Although relatively less investigated, DCs also possess the ability to integrate extracellular mechanical and immune stimuli and adapt their metabolic program to support processes involved in activation, migration, and antigen presentation. We favor a model where during acute inflammation or inflammatory diseases, where tissues undergo changes in physical properties, macrophages and DCs are not only activated by biochemical cues but also primed by mechanical signals ( Du et al, 2022 ). These innate immune cells detect mechanical forces through integrins connected to F-actin and ion channels Piezo1 and TRPV4.…”

Section: Discussionmentioning

confidence: 99%

Mechanosensing in macrophages and dendritic cells in steady-state and disease

Lee

Winer

et al. 2022

Front. Cell Dev. Biol.

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Macrophages and dendritic cells are myeloid cells that play critical roles in immune responses. Macrophages help to maintain homeostasis through tissue regeneration and the clearance of dead cells, but also mediate inflammatory processes against invading pathogens. As the most potent antigen-presenting cells, dendritic cells are important in connecting innate to adaptive immune responses via activation of T cells, and inducing tolerance under physiological conditions. While it is known that macrophages and dendritic cells respond to biochemical cues in the microenvironment, the role of extracellular mechanical stimuli is becoming increasingly apparent. Immune cell mechanotransduction is an emerging field, where accumulating evidence suggests a role for extracellular physical cues coming from tissue stiffness in promoting immune cell recruitment, activation, metabolism and inflammatory function. Additionally, many diseases such as pulmonary fibrosis, cardiovascular disease, cancer, and cirrhosis are associated with changes to the tissue biophysical environment. This review will discuss current knowledge about the effects of biophysical cues including matrix stiffness, topography, and mechanical forces on macrophage and dendritic cell behavior under steady-state and pathophysiological conditions. In addition, we will also provide insight on molecular mediators and signaling pathways important in macrophage and dendritic cell mechanotransduction.

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Section: Discussionmentioning

confidence: 99%

Mechanosensing in macrophages and dendritic cells in steady-state and disease

Lee

Winer

et al. 2022

Front. Cell Dev. Biol.

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“…The involvement of circulating immune cells in lung fibrosis is well recognized: among these cells are monocytes and neutrophils ( Ishikawa et al, 2021 ). While the details of recruitment and involvement of these cells are outside scope of this review, these processes can take place through both soluble mediators ( Huang et al, 2020 ; van Geffen et al, 2021 ) and mechanical factors ( Du et al, 2022 ). Higher counts of monocytes in blood were associated with faster disease progression in interstitial lung diseases ( Kim et al, 2022 ).…”

Section: A Hazardous Highway: Altered Ecm In Lung Diseases and Effect...mentioning

confidence: 99%

Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases

Joglekar

Nizamoglu²,

Fan³

et al. 2022

Front. Pharmacol.

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Environmental insults including respiratory infections, in combination with genetic predisposition, may lead to lung diseases such as chronic obstructive pulmonary disease, lung fibrosis, asthma, and acute respiratory distress syndrome. Common characteristics of these diseases are infiltration and activation of inflammatory cells and abnormal extracellular matrix (ECM) turnover, leading to tissue damage and impairments in lung function. The ECM provides three-dimensional (3D) architectural support to the lung and crucial biochemical and biophysical cues to the cells, directing cellular processes. As immune cells travel to reach any site of injury, they encounter the composition and various mechanical features of the ECM. Emerging evidence demonstrates the crucial role played by the local environment in recruiting immune cells and their function in lung diseases. Moreover, recent developments in the field have elucidated considerable differences in responses of immune cells in two-dimensional versus 3D modeling systems. Examining the effect of individual parameters of the ECM to study their effect independently and collectively in a 3D microenvironment will help in better understanding disease pathobiology. In this article, we discuss the importance of investigating cellular migration and recent advances in this field. Moreover, we summarize changes in the ECM in lung diseases and the potential impacts on infiltrating immune cell migration in these diseases. There has been compelling progress in this field that encourages further developments, such as advanced in vitro 3D modeling using native ECM-based models, patient-derived materials, and bioprinting. We conclude with an overview of these state-of-the-art methodologies, followed by a discussion on developing novel and innovative models and the practical challenges envisaged in implementing and utilizing these systems.

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“…For this narrative review, the exercise strategies considered involve walking, jogging, or running. PSS and/or circumferential wall stress or stretch (which arises from the effect of blood pressure on the vascular wall and is applied to all layers of the arterial wall) are the primary signals produced by EXER that are mechanically transduced by the EC [ 8 , 29 , 34 , 81 , 82 , 83 , 84 , 85 , 86 ].…”

Section: Exercisementioning

confidence: 99%

Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation; A Narrative Review

2022

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The monolayer of cells that line both the heart and the entire vasculature is the endothelial cell (EC). These cells respond to external and internal signals, producing a wide array of primary or secondary messengers involved in coagulation, vascular tone, inflammation, and cell-to-cell signaling. Endothelial cell activation is the process by which EC changes from a quiescent cell phenotype, which maintains cellular integrity, antithrombotic, and anti-inflammatory properties, to a phenotype that is prothrombotic, pro-inflammatory, and permeable, in addition to repair and leukocyte trafficking at the site of injury or infection. Pathological activation of EC leads to increased vascular permeability, thrombosis, and an uncontrolled inflammatory response that leads to endothelial dysfunction. This pathological activation can be observed during ischemia reperfusion injury (IRI) and sepsis. Shear stress (SS) and pulsatile shear stress (PSS) are produced by mechanical frictional forces of blood flow and contraction of the heart, respectively, and are well-known mechanical signals that affect EC function, morphology, and gene expression. PSS promotes EC homeostasis and cardiovascular health. The archetype of inducing PSS is exercise (i.e., jogging, which introduces pulsations to the body as a function of the foot striking the pavement), or mechanical devices which induce external pulsations to the body (Enhanced External Pulsation (EECP), Whole-body vibration (WBV), and Whole-body periodic acceleration (WBPA aka pGz)). The purpose of this narrative review is to focus on the aforementioned noninvasive methods to increase PSS, review how each of these modify specific diseases that have been shown to induce endothelial activation and microcirculatory dysfunction (Ischemia reperfusion injury-myocardial infarction and cardiac arrest and resuscitation), sepsis, and lipopolysaccharide-induced sepsis syndrome (LPS)), and review current evidence and insight into how each may modify endothelial activation and how these may be beneficial in the acute and chronic setting of endothelial activation and microvascular dysfunction.

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Tuning immunity through tissue mechanotransduction

Cited by 124 publications

References 195 publications

Mechanosensing in macrophages and dendritic cells in steady-state and disease

Mechanosensing in macrophages and dendritic cells in steady-state and disease

Highway to heal: Influence of altered extracellular matrix on infiltrating immune cells during acute and chronic lung diseases

Non-Invasive Pulsatile Shear Stress Modifies Endothelial Activation; A Narrative Review

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