p38 MAPK signaling mediates retinoic acid‐induced CD103 expression in human dendritic cells

Roe, Mandi M; Hashimi, Marziah; Swain, Steve D.; Woo, Krista M.; Bimczok, Diane

doi:10.1111/imm.13246

Cited by 10 publications

(5 citation statements)

References 46 publications

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“…Pellet by gentle centrifugation at 100 g for 2 min. 2) Preparation of MoDCs: a Prepare culture of MoDCs from blood monocytes using standard protocols ( Sebrell et al, 2019 ; Roe et al, 2020 ). b Harvest MoDCs by vigorous pipetting and washing with PBS.…”

Section: Methodsmentioning

confidence: 99%

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A Synthetic Hydrogel, VitroGel® ORGANOID-3, Improves Immune Cell-Epithelial Interactions in a Tissue Chip Co-Culture Model of Human Gastric Organoids and Dendritic Cells

et al. 2021

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Immunosurveillance of the gastrointestinal epithelium by mononuclear phagocytes (MNPs) is essential for maintaining gut health. However, studying the complex interplay between the human gastrointestinal epithelium and MNPs such as dendritic cells (DCs) is difficult, since traditional cell culture systems lack complexity, and animal models may not adequately represent human tissues. Microphysiological systems, or tissue chips, are an attractive alternative for these investigations, because they model functional features of specific tissues or organs using microscale culture platforms that recreate physiological tissue microenvironments. However, successful integration of multiple of tissue types on a tissue chip platform to reproduce physiological cell-cell interactions remains a challenge. We previously developed a tissue chip system, the gut organoid flow chip (GOFlowChip), for long term culture of 3-D pluripotent stem cell-derived human intestinal organoids. Here, we optimized the GOFlowChip platform to build a complex microphysiological immune-cell-epithelial cell co-culture model in order to study DC-epithelial interactions in human stomach. We first tested different tubing materials and chip configurations to optimize DC loading onto the GOFlowChip and demonstrated that DC culture on the GOFlowChip for up to 20 h did not impact DC activation status or viability. However, Transwell chemotaxis assays and live confocal imaging revealed that Matrigel, the extracellular matrix (ECM) material commonly used for organoid culture, prevented DC migration towards the organoids and the establishment of direct MNP-epithelial contacts. Therefore, we next evaluated DC chemotaxis through alternative ECM materials including Matrigel-collagen mixtures and synthetic hydrogels. A polysaccharide-based synthetic hydrogel, VitroGel®-ORGANOID-3 (V-ORG-3), enabled significantly increased DC chemotaxis through the matrix, supported organoid survival and growth, and did not significantly alter DC activation or viability. On the GOFlowChip, DCs that were flowed into the chip migrated rapidly through the V-ORG matrix and reached organoids embedded deep within the chip, with increased interactions between DCs and gastric organoids. The successful integration of DCs and V-ORG-3 embedded gastric organoids into the GOFlowChip platform now permits real-time imaging of MNP-epithelial interactions and other investigations of the complex interplay between gastrointestinal MNPs and epithelial cells in their response to pathogens, candidate drugs and mucosal vaccines.

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Section: Methodsmentioning

confidence: 99%

“…a Prepare culture of MoDCs from blood monocytes using standard protocols ( Sebrell et al, 2019 ; Roe et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

A Synthetic Hydrogel, VitroGel® ORGANOID-3, Improves Immune Cell-Epithelial Interactions in a Tissue Chip Co-Culture Model of Human Gastric Organoids and Dendritic Cells

et al. 2021

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“…Of course, other cellular signaling pathways besides GM-CSF are involved in regulating CD103 expression on cDCs. For example, TGFb and retinoic acid also reportedly induced CD103 expression (Iliev et al, 2009;Roe et al, 2017;Roe et al, 2020). Whether LPS and P. aeruginosa alter CD103 expression in response to these stimuli remains unknown, but definitely of interest.…”

Section: Discussionmentioning

confidence: 99%

Exposure to the Gram-Negative Bacteria Pseudomonas aeruginosa Influences the Lung Dendritic Cell Population Signature by Interfering With CD103 Expression

Brassard

Roy

Lemay

et al. 2021

Front. Cell. Infect. Microbiol.

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Lung dendritic cells (DCs) are divided into two major populations, which include CD103+XCR1+ cDC1s and CD11b+Sirpα+ cDC2s. The maintenance of their relative proportions is dynamic and lung inflammation, such as caused by exposure to lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, can have a significant impact on the local cDC signature. Alterations in the lung cDC signature could modify the capacity of the immune system to respond to various pathogens. We consequently aimed to assess the impact of the Gram-negative bacteria Pseudomonas aeruginosa on lung cDC1 and cDC2 populations, and to identify the mechanisms leading to alterations in cDC populations. We observed that exposure to P. aeruginosa decreased the proportions of CD103+XCR1+ cDC1s, while increasing that of CD11b+ DCs. We identified two potential mechanisms involved in this modulation of lung cDC populations. First, we observed an increase in bone marrow pre-DC IRF4 expression suggesting a higher propensity of pre-DCs to differentiate towards the cDC2 lineage. This observation was combined with a reduced capacity of lung XCR1+ DC1s to express CD103. In vitro, we demonstrated that GM-CSF-induced CD103 expression on cDCs depends on GM-CSF receptor internalization and RUNX1 activity. Furthermore, we observed that cDCs stimulation with LPS or P. aeruginosa reduced the proportions of intracellular GM-CSF receptor and decreased RUNX1 mRNA expression. Altogether, these results suggest that alterations in GM-CSF receptor intracellular localization and RUNX1 signaling could be involved in the reduced CD103 expression on cDC1 in response to P. aeruginosa. To verify whether the capacity of cDCs to express CD103 following P. aeruginosa exposure impacts the immune response, WT and Cd103-/- mice were exposed to P. aeruginosa. Lack of CD103 expression led to an increase in the number of neutrophils in the airways, suggesting that lack of CD103 expression on cDC1s could favor the innate immune response to this bacterium.

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“…It has been shown that activation of the p38 MAPK signaling pathway contributes to enhance PGC-1α level and promote mitochondrial biogenesis [ 29 ]. It has been shown that RA increases p38 MAPK phosphorylation level and improves its function [ 30 , 31 ]. Although several studies have revealed that VA and its metabolite (retinoic acid) affect myofiber type composition, whether VA affects the development of myofiber type in sheep is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK-PGC-1α signaling pathway and alters the muscle fiber composition of sheep

Song,

Zhao,

et al. 2024

J Animal Sci Biotechnol

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Background Vitamin A (VA) and its metabolite, retinoic acid (RA), are of great interest for their wide range of physiological functions. However, the regulatory contribution of VA to mitochondrial and muscle fiber composition in sheep has not been reported. Method Lambs were injected with 0 (control) or 7,500 IU VA palmitate into the biceps femoris muscle on d 2 after birth. At the age of 3 and 32 weeks, longissimus dorsi (LD) muscle samples were obtained to explore the effect of VA on myofiber type composition. In vitro, we investigated the effects of RA on myofiber type composition and intrinsic mechanisms. Results The proportion of type I myofiber was greatly increased in VA-treated sheep in LD muscle at harvest. VA greatly promoted mitochondrial biogenesis and function in LD muscle of sheep. Further exploration revealed that VA elevated PGC-1α mRNA and protein contents, and enhanced the level of p38 MAPK phosphorylation in LD muscle of sheep. In addition, the number of type I myofibers with RA treatment was significantly increased, and type IIx myofibers was significantly decreased in primary myoblasts. Consistent with in vivo experiment, RA significantly improved mitochondrial biogenesis and function in primary myoblasts of sheep. We then used si-PGC-1α to inhibit PGC-1α expression and found that si-PGC-1α significantly abrogated RA-induced the formation of type I myofibers, mitochondrial biogenesis, MitoTracker staining intensity, UQCRC1 and ATP5A1 expression, SDH activity, and enhanced the level of type IIx muscle fibers. These data suggested that RA improved mitochondrial biogenesis and function by promoting PGC-1α expression, and increased type I myofibers. In order to prove that the effect of RA on the level of PGC-1α is caused by p38 MAPK signaling, we inhibited the p38 MAPK signaling using a p38 MAPK inhibitor, which significantly reduced RA-induced PGC-1α and MyHC I levels. Conclusion VA promoted PGC-1α expression through the p38 MAPK signaling pathway, improved mitochondrial biogenesis, and altered the composition of muscle fiber type. Graphical Abstract

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p38 MAPK signaling mediates retinoic acid‐induced CD103 expression in human dendritic cells

Cited by 10 publications

References 46 publications

A Synthetic Hydrogel, VitroGel® ORGANOID-3, Improves Immune Cell-Epithelial Interactions in a Tissue Chip Co-Culture Model of Human Gastric Organoids and Dendritic Cells

A Synthetic Hydrogel, VitroGel® ORGANOID-3, Improves Immune Cell-Epithelial Interactions in a Tissue Chip Co-Culture Model of Human Gastric Organoids and Dendritic Cells

Exposure to the Gram-Negative Bacteria Pseudomonas aeruginosa Influences the Lung Dendritic Cell Population Signature by Interfering With CD103 Expression

Vitamin A regulates mitochondrial biogenesis and function through p38 MAPK-PGC-1α signaling pathway and alters the muscle fiber composition of sheep

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