Dataset Information

Tuning immunity through tissue mechanotransduction.

ABSTRACT: Immune responses are governed by signals from the tissue microenvironment, and in addition to biochemical signals, mechanical cues and forces arising from the tissue, its extracellular matrix and its constituent cells shape immune cell function. Indeed, changes in biophysical properties of tissue alter the mechanical signals experienced by cells in many disease conditions, in inflammatory states and in the context of ageing. These mechanical cues are converted into biochemical signals through the process of mechanotransduction, and multiple pathways of mechanotransduction have been identified in immune cells. Such pathways impact important cellular functions including cell activation, cytokine production, metabolism, proliferation and trafficking. Changes in tissue mechanics may also represent a new form of 'danger signal' that alerts the innate and adaptive immune systems to the possibility of injury or infection. Tissue mechanics can change temporally during an infection or inflammatory response, offering a novel layer of dynamic immune regulation. Here, we review the emerging field of mechanoimmunology, focusing on how mechanical cues at the scale of the tissue environment regulate immune cell behaviours to initiate, propagate and resolve the immune response.

SUBMITTER: Du H

PROVIDER: S-EPMC9379893 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Tuning immunity through tissue mechanotransduction.

Du Huixun H Bartleson Juliet M JM Butenko Sergei S Alonso Valentina V Liu Wendy F WF Winer Daniel A DA Butte Manish J MJ

Nature reviews. Immunology 20220816 3

Immune responses are governed by signals from the tissue microenvironment, and in addition to biochemical signals, mechanical cues and forces arising from the tissue, its extracellular matrix and its constituent cells shape immune cell function. Indeed, changes in biophysical properties of tissue alter the mechanical signals experienced by cells in many disease conditions, in inflammatory states and in the context of ageing. These mechanical cues are converted into biochemical signals through th ...[more]

PMID: 35974148

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Project description:Osteoclasts ubiquitously participate in bone homeostasis, and their aberration leads to bone diseases, such as osteoporosis. Current clinical strategies by biochemical signaling molecules often perturb innate bone metabolism owing to the uncontrolled management of osteoclasts. Thus, an alternative strategy of precise regulation for osteoclast differentiation is urgently needed. To this end, this study proposed an assumption that mechanic stimulation might be a potential strategy. Here, a hydrogel was created to imitate the physiological bone microenvironment, with stiffnesses ranging from 2.43kPa to 68.2kPa. The impact of matrix stiffness on osteoclast behaviors was thoroughly investigated. Results showed that matrix stiffness could be harnessed for directing osteoclast fate in vitro and in vivo. In particular, increased matrix stiffness inhibited the integrin β3-responsive RhoA-ROCK2-YAP-related mechanotransduction and promoted osteoclastogenesis. Notably, preosteoclast development is facilitated by medium-stiffness hydrogel (M-gel) possessing the same stiffness as vessel ranging from 17.5 kPa to 44.6 kPa by partial suppression of mechanotransduction, which subsequently encouraged revascularization and bone regeneration in mice with bone defects. Our works provide an innovative approach for finely regulating osteoclast differentiation by selecting the optimum matrix stiffness and enable us further to develop a matrix stiffness-based strategy for bone tissue engineering. Graphical abstract Matrix with stiffness similar to vessel halts the process of osteoclastogenesis at preosteoclast stage, which consequently promotes bone repair.Image 1 Highlights • Adjusting matrix stiffness could be an effective strategy to regulate osteoclast differentiation.• Matrix with higher stiffness enhanced osteoclast formation, and lower stiffness exhibited the opposite effect.• Vessel-like stiffness boosted preosteoclasts via integrin β3 and NF-κB signaling.• Vessel-like stiffness facilitated angiogenesis and osteogenesis by secreting PDGF-BB in bone defect.

Dataset Information

Tuning immunity through tissue mechanotransduction.

Publications

Tuning immunity through tissue mechanotransduction.

Similar Datasets

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