The Roles of Kidney-Resident ILC2 in Renal Inflammation and Fibrosis

Nagashima, Ryuichi; Iyoda, Masayuki

doi:10.3389/fimmu.2021.688647

Cited by 14 publications

(8 citation statements)

References 84 publications

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“…Some previous studies found that IL-33 expression was positively correlated with TGF-β (Li et al, 2014a;Kotsiou et al, 2018;Elsherbiny et al, 2020). This may be related to macrophages (Li et al, 2019b) or ILC2 (Nagashima and Iyoda, 2021). The specific link and mechanism between IL-33/ST2 and TFG-β need to be investigated further.…”

Section: Mechanisms Of Il33/st2 Involvement In Renal Fibrosismentioning

confidence: 92%

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

Tan

Jing

2022

Front. Physiol.

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Chronic kidney disease (CKD) is a major public health problem that affects more than 10% of the population worldwide and has a high mortality rate. Therefore, it is necessary to identify novel treatment strategies for CKD. Incidentally, renal fibrosis plays a central role in the progression of CKD to end-stage renal disease (ESRD). The activation of inflammatory pathways leads to the development of renal fibrosis. In fact, interleukin-33 (IL-33), a newly discovered member of the interleukin 1 (IL-1) cytokine family, is a crucial regulator of the inflammatory process. It exerts pro-inflammatory and pro-fibrotic effects via the suppression of tumorigenicity 2 (ST2) receptor, which, in turn, activates other inflammatory pathways. Although the role of this pathway in cardiac, pulmonary, and hepatic fibrotic diseases has been extensively studied, its precise role in renal fibrosis has not yet been completely elucidated. Recent studies have shown that a sustained activation of IL-33/ST2 pathway promotes the development of renal fibrosis. However, with prolonged research in this field, it is expected that the IL-33/ST2 pathway will be used as a diagnostic and prognostic tool for renal diseases. In addition, the IL-33/ST2 pathway seems to be a new target for the future treatment of CKD. Here, we review the mechanisms and potential applications of the IL-33/ST2 pathway in renal fibrosis; such that it can help clinicians and researchers to explore effective treatment options and develop novel medicines for CKD patients.

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Section: Mechanisms Of Il33/st2 Involvement In Renal Fibrosismentioning

confidence: 92%

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

Tan

Jing

2022

Front. Physiol.

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“…Indeed, IL5-producing ILC2s have been previously described in the perivascular space of large arteries 33 . They are known to be responsive to various local tissue factors, including cytokines, lipid mediators, neuropeptides, and hormones 34 . Prolonged activation through paracrine IL-33 stimulation was associated with arterial hypertrophy and eosinophilic inflammation in the lung 35 .…”

Section: Discussionmentioning

confidence: 99%

Microvascular immunity is organ-specific and concealed in peripheral blood

Rixen,

Schütz,

Walter

et al. 2024

Preprint

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Blood tests are a common method for diagnosing and monitoring various health conditions. Nevertheless, the extent to which phlebotomy can offer insights into immune and organ dysfunction remains uncertain. Here, we conducted a comprehensive analysis of blood-borne leukocytes in the microvasculature of different mouse organs and compared it to peripheral blood and parenchymal samples. We observed that microvascular immune cells outnumber tissue-resident counterparts in the kidney, liver and lung. Classical monocytes and lymphocytes are diminished while nonclassical and SSC-high monocytes are enriched compared to blood. Utilizing single-cell sequencing, we identified specific cell populations up to 100-fold expanded in the kidney vasculature including macrophages, plasmacytoid dendritic cells, B cells, and innate lymphoid cells type 2. Microvascular enrichment could trigger a local phenotype switch as shown in glomerulus-restricted B cells. Peritonitis and acute kidney injury (AKI) elicited a multifaceted and systemic response of microvascular leukocytes. It involved remote organ effects, such as a 16-fold increase of leukocytes in the splenic circulation or 64-fold increase of SSC-high monocytes in the liver circulation that was not detectable in the peripheral blood or the tissue. Following full recovery from AKI, persistent and complex changes were observed predominantly in the renal vasculature, while most leukocytes in the peripheral blood had already returned to baseline levels. Collectively, our findings suggest a paradigm of organ- and disease-specific microvascular immunity that largely eludes conventional blood and tissue analysis.

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“…Excessive extracellular matrix deposition and chronic inflammation can lead to renal fibrosis, end-stage renal disease, and renal failure [ 26 ]. The TGF-β1/Smad signaling pathway causes inflammation, EMT, and abnormal extracellular matrix deposition to promote renal fibrosis [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels

et al. 2022

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Background Renal tubular epithelial–myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-β1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs. Method HK-2, a human RTEC line, was co-treated with TGF-β1 and hucMSC-derived exosomes. Additionally, TGF-β1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively. Results TGF-β1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1β, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-β1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-β1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind the ADAM19 3′-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-β1 induction. Conclusions HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-β1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.

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The Roles of Kidney-Resident ILC2 in Renal Inflammation and Fibrosis

Cited by 14 publications

References 84 publications

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

Interleukin-33/ Suppression of Tumorigenicity 2 in Renal Fibrosis: Emerging Roles in Prognosis and Treatment

Microvascular immunity is organ-specific and concealed in peripheral blood

Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels

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