Analysis of serum and salivary cytokines among patients with oral cGVHD after Allo‐HSCT

Yong, Xiangzhi; Peng, Yan; Liu, Zhenmin; Li, Qiaochuan; Lai, Yue‐Yun; Wu, Tiantian; Tao, Renchuan

doi:10.1111/odi.13658

Cited by 8 publications

(14 citation statements)

References 16 publications

(15 reference statements)

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“…In the present study, of all 28 genes examined, the transcriptional level of 20 genes showed more than a ten-fold difference between presence and absence of oral GVHD, agreeing with [9]. TNF, IL-1β, IFN-γ and CCL2 show the highest expression level in the oGVHD group.…”

Section: Discussionsupporting

confidence: 89%

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Gene expression profile of chronic oral graft-versus-host disease

et al. 2022

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Among the complications observed after allogeneic hematopoietic stem cell transplantation, graft-versus-host disease (GVHD) is the primary cause of post-transplant mortality. The oral cavity is the second most affected organ target in chronic GVHD. Tissue damage results from the upregulation of inflammatory mediators, which play a critical role in the immunopathogenesis of the disease. This case series observational study aims to evaluate the participation of cytokines, chemokines, transcription factors, and heat shock proteins in the pathogenesis of oral GVHD (oGVHD), describing the mRNA expression of 28 genes selected. Peripheral blood mononuclear cells were isolated from six participants with oGVHD and two without GVHD, and relative expression of transcripts with established roles as inflammatory mediators was determined in triplicate using the human RT2 Profiler™ PCR Array. The gene expression levels in the group with oGVHD were mainly up-regulated compared to those without GVHD. PBMC from oGVDH expressed consistently higher IFN-γ, TNF, IL-1β, CCL2, HSP60 (HSPD1) and HSP90 (HSP90B1). These results can provide a basis for developing new molecular diagnostics and targets therapies for the clinical management of oGVHD.

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Section: Discussionsupporting

confidence: 89%

“…Recently, the loss of dental microbiota was associated with the risk and intensity of acute GVHD but not with other allo-HSCT outcomes, such as oral chronic GVHD [8]. In contrast, Yong et al, 2021 suggest that serum cytokines rather than cytokine-secreting cells were involved in driving and maintaining oral GVHD [9].…”

Section: Introductionmentioning

confidence: 99%

Gene expression profile of chronic oral graft-versus-host disease

et al. 2022

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“…IL-17 + cells were identified in skin, all oral mucosa and gut biopsies, and were found more frequently in mucosa lesions than in skin 28. In our previous study, we found level of transforming growth factorβ(TGF-β) in serum, the key cytokines of Tregs are influential factors of occurrence of oral cGVHD 29. In addition, T lymphocytes invade the MSGs in oral mucosa in our model, unlike oral lichen planus.The immunological features of oral mucosa and salivary glands in our model are somewhat consistent with human oral cGVHD described within those studies.…”

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confidence: 63%

The oral histopathological and immunological characteristics of a xenogeneic mouse chronic graft‐versus‐host disease model

Jiang

Yong

Liu

et al. 2021

J Oral Pathology Medicine

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Background Oral lesions are important clinical manifestations of chronic graft‐verse‐host disease (cGVHD). However, the oral characteristics of cGVHD mouse model are not yet clear. This study aims to demonstrate oral histopathological and immunological characteristics of a xenogeneic cGVHD mouse model. Materials and methods 2.5 × 106, 5.0 × 106, 7.5 × 106, and 10.0 × 106 human peripheral blood mononuclear cells (hPBMCs) were intravenously transplanted into NCG mice to induce cGVHD. After transplantation, clinical observations were recorded. Tissue samples from salivary glands and oral mucosa were stained with H&E, Masson Trichrome, and immunofluorescence, and the histopathology of oral tissues was scored according to our modified criteria. Results NCG mice showed signs of cGVHD onset after transplantation. The oral histopathological lesion incidences in each group were 37.50%, 50.00%, 62.50%, and 75.00%, respectively. Oral histopathological lesion incidence and histopathological scores were positively correlated with the amount of infused hPBMCs. Epithelial atrophy, epithelial cells vacuolar degeneration, and basal cells liquefaction denaturation were observed in oral mucosa, and acinar destruction and collagen deposition were observed in the salivary glands. Human CD45+, CD4+, CD8+, IL‐17+, and FoxP3+ cells infiltrated into oral tissues. In the 5.0 × 106 hPBMCs group, oral histopathological changes mainly began between days 30 and 45 post‐transplantation, and became more severe after day 45. The oral histopathological scores also gradually increased. Conclusion Inflammation in oral mucosa epithelium and salivary glands, and CD4+ and CD8+ T cells dominating infiltration are the main oral features in the xenogeneic cGVHD mouse model. The severity of oral histopathological lesions shows a dose and time correlation. These may be helpful to oral cGVHD research.

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“…Bioinformatics analysis of miRNA-769-5p showed that target genes of it were mainly concentrated in the TGF-β signaling pathway. TGF-β was found to in uence the occurrence of oral cGVHD in our previous study [24], so we concentrated on the TGF-β/Smads signaling pathway as a result of the ndings. TGF-β/Smads signaling pathway could promote the Th17 immunoreaction [25] and tissue brosis[26] after activation with phosphorylated TβR combined to Smad 2[27].Smads could be modulated by miRNAs [28,29].…”

Section: Discussionmentioning

confidence: 99%

miRNA-769-5p and Smad2 Differential Expression in Patients with or without Oral cGVHD

Yong

Zhou

Jiang

et al. 2023

Preprint

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Background: Oral chronic graft versus host disease (Oral cGVHD) affects the life quality of patient. But its pathogenesis is still unclear. MicroRNA (miRNA) involves in numerous pathologic and physiologic processes. Objective: To preliminarily observe the change of miRNAs in oral cGVHD. Methods: Peripheral venous blood was taken from 8 cases of oral cGVHD, 8 cases without oral cGVHD, and 8 cases of healthy control group to construct the miRNAs library by Illumina Hiseq 2500 platform. The expression of miRNA-769-5p was detected by qRT-PCR in each group with subjects adding to 15. The interactions between miRNA-769-5p and Smad2 mRNA was verified by dual-luciferase assay. qRT-PCR and ELISA was used to detect the mRNA and protein level of Smad2 in peripheral blood respectively. Results: All three groups expressed 518 miRNAs and 191 miRNAs showed significantly different expression. The expression of miRNA-769-5p was the higher in non-oral cGVHD patients than that in oral cGVHD patients, and were of certain value in the diagnosis of oral cGVHD. The levels of Smad2 mRNA and protein were higher in the oral cGVHD group than those without oral cGVHD. As a target of miRNA-769-5p, Smad2 mRNA was negatively related to it. Conclusion: Differential expression of miRNAs, especially miRNA-769-5p may be involved in oral cGVHD. High expression of circulating Smad2 may be associated with the oral cGVHD, which might be regulated by miRNA-769-5p.

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Analysis of serum and salivary cytokines among patients with oral cGVHD after Allo‐HSCT

Cited by 8 publications

References 16 publications

Gene expression profile of chronic oral graft-versus-host disease

Gene expression profile of chronic oral graft-versus-host disease

The oral histopathological and immunological characteristics of a xenogeneic mouse chronic graft‐versus‐host disease model

miRNA-769-5p and Smad2 Differential Expression in Patients with or without Oral cGVHD

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