Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

Wiśnicki, Krzysztof; Donizy, Piotr; Remiorz, Agata; Janczak, Dariusz; Krajewska, Magdalena; Banasik, Mirosław

doi:10.3390/diagnostics12102353

Cited by 5 publications

(4 citation statements)

References 90 publications

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“…Those lacking IDO1 demonstrated a significantly higher risk of rejection, with rejection rates reaching 62.2%, while IDO1(+) positive patients experienced lower rejection rates at 32.9%. This statistically significant difference highlights the clinical relevance of IDO1 as a potential biomarker for assessing rejection risk in kidney transplant recipients, and it corroborates our previous summary [13]. Our study's impact is further emphasized by the distinct associations between IDO1 expression and specific rejection types.…”

Section: Discussionsupporting

confidence: 89%

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Indoleamine 2,3-Dioxygenase 1 (IDO1) in Kidney Transplantation: A Guardian against Rejection

Wiśnicki,

Donizy,

Hałoń

et al. 2023

JCM

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Kidney transplantation is a crucial treatment for end-stage kidney disease, with immunosuppressive drugs helping to reduce acute rejection rates. However, kidney graft longevity remains a concern. This study explores the role of indoleamine 2,3-dioxygenase 1 (IDO1) in kidney transplant immunology. IDO1 breaks down tryptophan, affecting immune cell behavior, primarily T-cells. The research focuses on both cellular and antibody-mediated immune responses, often causing graft damage. The study assessed IDO1 expression in renal transplant biopsies from patients with graft function decline, examining its connection to clinical parameters. A total of 121 biopsy samples were evaluated for IDO1 expression using immunohistochemistry. Patients were categorized as IDO1(+) positive or IDO1(−) negative based on immunoreactivity in tubular epithelium. Results showed a significant link between IDO1 expression and rejection incidence. IDO1(+) positive patients had lower rejection rates (32.9%) compared to IDO1(−) negative ones (62.2%) [p = 0.0017], with substantial differences in antibody-mediated rejection (AMR) (5.2% vs. 20%) [p = 0.0085] and T-cell mediated rejection (TCMR) (31.6% vs. 57.8%). These associations suggest that IDO1 may play a protective role in kidney transplant rejection. IDO1 modulation could offer novel therapeutic avenues to enhance graft survival. The study underscores IDO1 as a potential marker for rejection risk assessment, with its potential applications in personalized interventions and improved patient outcomes. Further research is needed to fully comprehend the mechanisms behind IDO1’s immunomodulatory functions and its potential clinical translation.

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Section: Discussionsupporting

confidence: 89%

“…In a review that we have published [13], we have summarized the mechanisms associated with IDO1 and outlined its significance in the immunological response of kidney graft recipients [14]. Indoleamine 2,3-dioxygenase (IDO1) is an intracellular enzyme that breaks down tryptophan to produce kynurenine metabolites [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Indoleamine 2,3-Dioxygenase 1 (IDO1) in Kidney Transplantation: A Guardian against Rejection

Wiśnicki,

Donizy,

Hałoń

et al. 2023

JCM

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“…IDO1 is primarily expressed in immune cells, such as DCs, macrophages, and monocytes. It plays a crucial role in immune tolerance and immune escape mechanisms by regulating the balance between immune activation and suppression 20 , 21 . Our previous research has also affirmed that exosomes (Exos) derived from overexpression IDO1 BMSCs enhance the immunotolerance of cardiac allografts 22 .…”

Section: Introductionmentioning

confidence: 99%

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs

Zheng,

Wu,

et al. 2024

Cell Transplant

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Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow–derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.

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“…The rate-limiting enzyme is indoleamine 2,3-dioxygenase a key enzyme responsible for tryptophan/kynurenine transformation. This step is potentially regulated by interferon activity thus providing a negative feedback loop during immune stimulation [3]. This may bring many pathophysiological consequences.…”

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confidence: 99%

I feel it in my fingers, I feel it in my toes, rheumatism that’s all around me…

Buc-Piorun,

Samborski,

Kotyla

2023

Rheumatology Forum

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Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients

Cited by 5 publications

References 90 publications

Indoleamine 2,3-Dioxygenase 1 (IDO1) in Kidney Transplantation: A Guardian against Rejection

Indoleamine 2,3-Dioxygenase 1 (IDO1) in Kidney Transplantation: A Guardian against Rejection

Mechanism Exploration on the Immunoregulation of Allogeneic Heart Transplantation Rejection in Rats With Exosome miRNA and Proteins From Overexpressed IDO1 BMSCs

I feel it in my fingers, I feel it in my toes, rheumatism that’s all around me…

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