Murine cytomegalovirus promotes renal allograft inflammation via Th1/17 cells and IL-17A

Dhital, Ravi; Anand, Shashi; Graber, Brianna; Zeng, Qiang; Velazquez, Victoria M.; Boddeda, Srinivasa Rao; Fitch, James; Minz, Ranjana W.; Minz, Mukut; Sharma, Ashish; Cianciolo, Rachel E.; Shimamura, Masako

doi:10.1111/ajt.17116

Cited by 8 publications

(2 citation statements)

References 144 publications

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“…However, some transcriptional programming was tissue-specific for the allograft, including Il17a and Junb expression. JunB was reported to contribute to Th17 cell pathogenicity ( 34 ), and Th17 cells are abundant in allografts during acute rejection and are associated with graft failure ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts

Zhang,

Cavazzoni,

Podestà

et al. 2023

JCI Insight

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Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins, and functions of Tfh cells in this process have not been fully characterized. Here we show that a subset of effector Tfh cells marked by previous IL-21 production is potently induced during allogeneic kidney transplantation and is inhibited by immunosuppressive agents. Single-cell RNA-Seq revealed that these lymph node (LN) effector Tfh cells have transcriptional and clonal overlap with IL-21–producing kidney-infiltrating Tfh cells, implicating common origins and developmental trajectories. To investigate the precise functions of IL-21–producing effector Tfh cells in LNs and allografts, we used a mouse model to selectively eliminate these cells and assessed allogeneic B cell clonal dynamics using a single B cell culture system. We found that IL-21–producing effector Tfh cells were essential for transplant rejection by regulating donor-specific germinal center B cell clonal dynamics both systemically in the draining LN and locally within kidney grafts. Thus, IL-21–producing effector Tfh cells have multifaceted roles in Ab-mediated rejection after kidney transplantation by promoting B cell alloimmunity.

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Section: Discussionmentioning

confidence: 99%

IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts

Zhang,

Cavazzoni,

Podestà

et al. 2023

JCI Insight

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“…For example, in systemic lupus erythematosus (SLE), excessive differentiation of Th17 cells and reduced differentiation of Treg cells are the main causes of disease development and tissue damage (8). Besides, Th1 and Th17 cells are closely related to the occurrence of this pathological state in acute cellular rejection induced by organ transplantation (9). Hence, it is crucial to restore the equilibrium of different subtypes of CD4 + T cells in diseases and stabilize it in healthy organisms.…”

Section: Introductionmentioning

confidence: 99%

Glutaminolysis and peripheral CD4+ T cell differentiation: from mechanism to intervention strategy

Liu¹,

Ren²,

Sun³

et al. 2023

Front. Immunol.

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To maintain the body’s regular immune system, CD4+ T cell homeostasis is crucial, particularly T helper (Th1, Th17) cells and T regulatory (Treg) cells. Abnormally differentiated peripheral CD4+ T cells are responsible for the occurrence and development of numerous diseases, including autoimmune diseases, transplantation rejection, and irritability. Searching for an effective interventional approach to control this abnormal differentiation is therefore especially important. As immunometabolism progressed, the inherent metabolic factors underlying the immune cell differentiation have gradually come to light. Mounting number of studies have revealed that glutaminolysis plays an indelible role in the differentiation of CD4+ T cells. Besides, alterations in the glutaminolysis can also lead to changes in the fate of peripheral CD4+ T cells. All of this indicate that the glutaminolysis pathway has excellent potential for interventional regulation of CD4+ T cells differentiation. Here, we summarized the process by which glutaminolysis regulates the fate of CD4+ T cells during differentiation and further investigated how to reshape abnormal CD4+ T cell differentiation by targeting glutaminolysis.

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A Two‐Center Study of a Prognostic Model Related to Acute Kidney Injury After Allogeneic Hematopoietic Stem Cell Transplantation in Children: Development of a New Predictive Dynamic Nomogram

Chen,

Jia,

Guo

et al. 2024

Pediatric Blood & Cancer

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ObjectivesThe purpose of this study was to develop a straightforward, easy‐to‐use online dynamic nomogram for the identification of children who are at high risk of developing acute kidney injury (AKI) after allogeneic hematopoietic stem cell transplantation (allo‐HSCT).MethodsThis was a two‐center study in which 242 children in Henan Provincial Children's Hospital composed the training cohort, and 115 children in the First Affiliated Hospital of Zhengzhou University composed the validation cohort. Kaplan–Meier survival analysis was used to compare survival between children with nonacute kidney injury (NAKI) and children with AKI. Multivariate logistic regression analysis was used to identify risk factors for AKI in children who underwent HSCT. The selected variables were utilized to construct nomograms, which were validated via the concordance index (C‐index), decision curve analysis, calibration curve analysis, and receiver operating characteristic (ROC) curve analysis.ResultsCumulative survival was significantly lower in children with AKI than in children without kidney injury (p < 0.01). Eight variables were included in the nomogram: hepatic veno‐occlusive disease (HVOD), graft‐versus‐host disease (GVHD), ferritin, C‐reactive protein (CRP), Cytomegalovirus infection (CMV), thrombotic microangiopathy (TMA), human leukocyte antigen (HLA), and nephrotoxic drugs. The nomogram calibration curves in the training and validation cohorts were highly comparable to the standard curves. The areas under the curve (AUCs) of the prediction model were 0.963 and 0.910 in the training cohort and validation cohort, respectively. The decision curve analysis (DCA) revealed that the model had a significant clinical benefit.ConclusionsThe occurrence of AKI affects the prognosis of children who undergo HSCT. We developed a dynamic online nomogram for predicting AKI in children who underwent allo‐HSCT on the basis of eight variables. The predictive value and clinical benefit of the nomogram model were acceptable.

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Murine cytomegalovirus promotes renal allograft inflammation via Th1/17 cells and IL-17A

Cited by 8 publications

References 144 publications

IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts

IL-21–producing effector Tfh cells promote B cell alloimmunity in lymph nodes and kidney allografts

Glutaminolysis and peripheral CD4+ T cell differentiation: from mechanism to intervention strategy

A Two‐Center Study of a Prognostic Model Related to Acute Kidney Injury After Allogeneic Hematopoietic Stem Cell Transplantation in Children: Development of a New Predictive Dynamic Nomogram

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