Effects of recombinant human interleukin-10 on Treg cells, IL-10 and TGF-β in transplantation of rabbit skin

Liu, Kai Shan; Fan, Xiao Qin; Zhang, Lei; Wen, Qiong; Feng, Ji Hong; Chen, Fu Chao; Luo, Jun; Sun, Wan Bang

doi:10.3892/mmr.2013.1817

Cited by 10 publications

(9 citation statements)

References 16 publications

(18 reference statements)

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“…IL-10 is an anti-inflammatory, anti-fibrotic immunoregulatory cytokine, which attenuates alloimmune response and displays pleiotropic effects on both innate and adaptive immunity [ 24 , 25 , 26 , 33 , 60 , 61 , 62 ]. Several experimental studies have demonstrated that IL-10 administration before transplantation facilitates tissue repair and graft survival [ 43 , 63 , 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…IL-10-mediated immune modulation and protection have been demonstrated in preclinical and clinical studies which highlighted the key immunosuppressive, protective, and antifibrotic roles of IL-10 in delaying the progression of fibrosis after transplantation [ 25 , 31 , 43 , 87 ]. IL-10 inhibits ischemia/reperfusion injury [ 78 , 88 ], prolongs allograft survival [ 61 , 87 ], and is essential for the action of Tregs mediating tolerance in different transplant models [ 28 , 62 , 89 , 90 ]. Besides, IL-10 is required for the immunoregulatory activity of Tregs as reported in the mouse model of skin transplantation, which demonstrated that blockade of IL-10 pathways abrogated immunoregulation mediated by CD25 + T cells [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

“…Besides, IL-10 is required for the immunoregulatory activity of Tregs as reported in the mouse model of skin transplantation, which demonstrated that blockade of IL-10 pathways abrogated immunoregulation mediated by CD25 + T cells [ 91 ]. Further studies in a rabbit model of skin transplantation demonstrated the key roles of IL-10 and Treg association during rejection, which concluded that IL-10 delayed the rejection time and thus prolonged the allograft survival time [ 43 , 61 , 87 ]. As reported earlier, IL-10 signaling affects the generation and function of Treg during tolerance through IL-10 receptors in Treg cells, and that signaling is required for Th17-mediated inflammation and subdues the toxic effects of inflammatory mediators during an immune reaction [ 24 , 90 , 92 ].…”

Section: Discussionmentioning

confidence: 99%

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IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts

Khan

Ashoor

Shamma

et al. 2021

Cells

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Interleukin-10 plays a vital role in maintaining peripheral immunotolerance and favors a regulatory immune milieu through the suppression of T effector cells. Inflammation-induced microvascular loss has been associated with airway epithelial injury, which is a key pathological source of graft malfunctioning and subepithelial fibrosis in rejecting allografts. The regulatory immune phase maneuvers alloimmune inflammation through various regulatory modulators, and thereby promotes graft microvascular repair and suppresses the progression of fibrosis after transplantation. The present study was designed to investigate the therapeutic impact of IL-10 on immunotolerance, in particular, the reparative microenvironment, which negates airway epithelial injury, and fibrosis in a mouse model of airway graft rejection. Here, we depleted and reconstituted IL-10, and serially monitored the phase of immunotolerance, graft microvasculature, inflammatory cytokines, airway epithelium, and subepithelial collagen in rejecting airway transplants. We demonstrated that the IL-10 depletion suppresses FOXP3+ Tregs, tumor necrosis factor-inducible gene 6 protein (TSG-6), graft microvasculature, and establishes a pro-inflammatory phase, which augments airway epithelial injury and subepithelial collagen deposition while the IL-10 reconstitution facilitates FOXP3+ Tregs, TSG-6 deposition, graft microvasculature, and thereby favors airway epithelial repair and subepithelial collagen suppression. These findings establish a potential reparative modulation of IL-10-associated immunotolerance on microvascular, epithelial, and fibrotic remodeling, which could provide a vital therapeutic option to rescue rejecting transplants in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts

Khan

Ashoor

Shamma

et al. 2021

Cells

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“…In addition, IL-10 can assist the differentiation of infantile T cells into Treg cells, while Treg cells can secrete IL-10. Positive feedback regulation between Treg cells and IL-10 may promote immune tolerance ( 60 – 62 ). Therefore, AFP can cause upregulation of Fas and FasL expression in Treg cells and promote the secretion of IL-10 by PD-1/PD-L signaling, leading to the inhibition of the proliferation of CD8 + T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

High lymphocyte‑to‑monocyte ratio is associated with low α‑fetoprotein expression in patients with hepatitis B virus‑associated hepatocellular carcinoma

Wang

et al. 2020

Mol Med Rep

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The association of the peripheral lymphocyte-to-monocyte ratio (lMr) with α-fetoprotein (aFP) status in patients with aFP-positive and aFP-negative hepatocellular carcinoma (Hcc) has not been investigated in detail. The aim of the present study was to examine the association between the lMr and aFP status in these patients. The samples were obtained from patients with a hepatitis B virus (HBV) infection, who were negative for non-HBV hepatitis viruses and who did not suffer from autoimmune hepatitis. These patients were retrospectively reviewed and the differences of test indicators in the aFP-negative and aFP-positive groups were assessed. Flow cytometry was used to detect the expression levels of cd4, cd8 and programmed cell death protein 1 (Pd-1), and eliSas were used to analyze the expression levels of interleukin (il)-10 and transforming growth factor (TGF)-β1. in addition, luciferase reporter assays were used to assess binding of the il-10 promoter to the glucocorticoid receptor (Gr) gene. receiver operating characteristic curve and Spearman correlation analyses demonstrated that the aFP-negative Hcc group exhibited a higher LMR, lower D-dimer and lower fibrin degradation products compared with the aFP-positive Hcc group. The cutoff value of the lMr was 2.01 for aFP detection, with a sensitivity of 68.6% and a specificity of 75%. The high LMR noted in the aFP-negative Hcc group was accompanied by a lower proportion of cd4 + T lymphocytes and cd8-Pd-1 expression compared with the corresponding levels of these parameters in the aFP-positive Hcc group. Furthermore, the high levels of il-10 and low levels of TGF-β1 were expressed in the aFP-positive Hcc group. The data indicated that the IL-10-592 promoter exhibited a potent induction of luciferase activity in 293T cells cotransfected with a GR-overexpressing vector compared with the control cells. However, the relative luciferase activity was not altered following a mutation or polymorphism in the il-10 gene. These results suggested that a high lMr was indicative of low aFP expression in HBV-associated Hcc patients.

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“…IL-10 has been reported to modulate regulatory T cells (Tregs) and conserve FOXP3 expression and associated suppressive function [3,4]. In addition, IL-10 influences wound healing, tissue repair, angiogenesis, and antifibrotic properties as reported in several preclinical studies including transplantation [2,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts

Kazmi

Khan

Shamma

et al. 2022

IJMS

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Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (−) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and β-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and β-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and β-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (−) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, β-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings.

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Effects of recombinant human interleukin-10 on Treg cells, IL-10 and TGF-β in transplantation of rabbit skin

Cited by 10 publications

References 16 publications

IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts

IL-10 Mediated Immunomodulation Limits Subepithelial Fibrosis and Repairs Airway Epithelium in Rejecting Airway Allografts

High lymphocyte‑to‑monocyte ratio is associated with low α‑fetoprotein expression in patients with hepatitis B virus‑associated hepatocellular carcinoma

Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts

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