Resolution of acute intestinal graft-versus-host disease

Thiagarajan, Sindhu; Hildner, Kai

doi:10.1007/s00281-019-00769-w

Cited by 8 publications

(5 citation statements)

References 71 publications

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“…IL-17 has been confirmed to play an important role in maintaining the integrity of the intestinal mucosa (1,12). From the above results, we inferred that the influence of intestinal flora on gut aGVHD mainly involved the activation of MAIT cells through its riboflavin metabolic pathway (MR1 pathway), and then the activated MAIT cells can resist the occurrence of gut aGVHD by secreting IL-17.…”

Section: Discussionmentioning

confidence: 84%

“…Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality (1)(2)(3)(4)(5). Its pathogenesis mainly involves the activation of donor T cells, which cause cytokine storm-inflammatory damage and attack the host's intestinal tissues (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…Systemic irradiation and chemotherapy before allo-HSCT can cause intestinal mucosal damage, resulting in the loss of integrity of the intestinal epithelial barrier. These injuries can also lead to the release of interleukin (IL)-17 and other protective cytokines induced by microbiogenic antigens whose main function is to limit the transmission of pathogens (1,(12)(13)(14). For patients with gut aGVHD, as further damage to the integrity of the intestinal epithelium is caused by aGVHD, the intestinal flora becomes ecologically unbalanced, and the diversity of the flora is significantly reduced (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

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The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

Gao

Hong

Zhao

et al. 2021

Blood

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Background & Purpose: Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosal-associated invariant T cells (MAITs) are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT in the occurrence of gut aGVHD in the human body. Methods & Cases: In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells (MAITs) and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyse the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAITs. The number and distribution of MAITs in intestinal tissues were analysed by immunofluorescence technology. We prospectively studied the enrolled 150 consecutive patients who underwent allo-HSCT in our institute. Results: The number and frequency of MAITs in infused grafts in gut aGVHD patients were lower than those in non-gut aGVHD patients (Figure). Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early post-transplantation period (+14 days). At the onset of gut aGVHD, the number of MAITs decreased in peripheral blood, and the activation marker CD69, chemokines CXCR3 and CXCR4 and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAITs secreted more granzyme B, TNF-α and IFN-γ under the stimulation of IL-12/IL-18 (non-TCR signal) and secreted most of the IL-17 under the stimulation of CD3/CD28 (TCR signal). MAITs inhibited the proliferation of CD4+ T cells in vitro. Conclusions: In conclusion, the lower number of MAITs in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAITs in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAITs and promoted the secretion of intestinal protective factors to affect the occurrence of gut aGVHD in humans. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

Gao

Hong

Zhao

et al. 2021

Blood

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“…Studies have confirmed that changes in bilirubin and ALT are the most important manifestations of liver GVHD. Additionally, changes in the levels of bilirubin and/or ALT and GGT prior to the manifestation of the liver GVHD can be a sign of future liver GVHD in the guideline [ 27 ]. Interestingly, our research found that the liver index most closely related to ocular GVHD was GGT; this index has also been shown to be related to inflammatory disease and reactive oxygen species (ROS) production [ 28 ], and thus we speculate that changes in GGT may be related to liver inflammation in early liver GVHD.…”

Section: Discussionmentioning

confidence: 99%

A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors

et al. 2023

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Objective To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). Methods This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. Results Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895–1.000) and 0.969 (95% CI, 0.846–1.000), respectively.And the Hosmer–Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). Conclusion We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.

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“…In vitro studies have shown that MAIT cells can transform into MAIT17 subsets or secrete increased IL-17 upon stimulation with TCR-specific (riboflavin metabolite 5-OP-RU or E. coli ) or nonspecific signals (CD3/CD28) ( 14 , 20 , 47 , 48 ). IL-17 has been shown to play an important role in maintaining the integrity of the intestinal mucosa ( 14 , 26 , 49 – 51 ). RNA-seq technology analysis also confirmed that, under TCR stimulation, upregulated IL-17F expression and a large number of genes associated with tissue repair characteristics were observed, including Furin , TNF , CSF1 , and CCL3 and other genes as well as various growth factors ( 21 , 52 ).…”

Section: The Immune Regulation Of Mait Cells In Hematopoietic Stem Ce...mentioning

confidence: 99%

Mining the multifunction of mucosal-associated invariant T cells in hematological malignancies and transplantation immunity: A promising hexagon soldier in immunomodulatory

Gao

Zhao

2022

Front. Immunol.

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Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved innate-like T cells capable of recognizing bacterial and fungal ligands derived from vitamin B biosynthesis. Under different stimulation conditions, MAIT cells can display different immune effector phenotypes, exerting immune regulation and anti-/protumor responses. Based on basic biological characteristics, including the enrichment of mucosal tissue, the secretion of mucosal repair protective factors (interleukin-17, etc.), and the activation of riboflavin metabolites by intestinal flora, MAIT cells may play an important role in the immune regulation effect of mucosal lesions or inflammation. At the same time, activated MAIT cells secrete granzyme B, perforin, interferon γ, and other toxic cytokines, which can mediate anti-tumor effects. In addition, since a variety of hematological malignancies express the targets of MAIT cell-specific effector molecules, MAIT cells are also a potentially attractive target for cell therapy or immunotherapy for hematological malignancies. In this review, we will provide an overview of MAIT research related to blood system diseases and discuss the possible immunomodulatory or anti-tumor roles that unique biological characteristics or effector phenotypes may play in hematological diseases.

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Resolution of acute intestinal graft-versus-host disease

Cited by 8 publications

References 71 publications

The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

The Potential Roles of Mucosa-Associated Invariant T Cells in the Pathogenesis of Gut Graft-Versus-Host Disease after Hematopoietic Stem Cell Transplantation

A nomogram model for predicting ocular GVHD following allo-HSCT based on risk factors

Mining the multifunction of mucosal-associated invariant T cells in hematological malignancies and transplantation immunity: A promising hexagon soldier in immunomodulatory

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