The mast cell: A Janus in kidney transplants

Elst, G. van der; Varol, Hilal; Hermans, Maud A.W.; Baan, Carla C.; Huyen, J. P. Duong-van; Hesselink, Dennis A.; Kramann, Rafael; Rabant, Marion; Reinders, Marlies E.J.; Thüsen, Jan H. von der; Bosch, Thierry P P van den; Groningen, Marian C. Clahsen-van

doi:10.3389/fimmu.2023.1122409

Cited by 3 publications

(5 citation statements)

References 133 publications

(190 reference statements)

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“…We also performed immune infiltration analysis to identify the immune changes in AKI. The results showed that AKI mice had a higher levels of gamma delta T cells ( Hochegger et al, 2007 ), CD4 memory resting cells T cells ( Farooqui et al, 2023 ), resting mast cells ( van der Elst et al, 2023 ), and M2 macrophages ( Li et al, 2018 ; Singbartl et al, 2019 ). It has been reported that the gamma delta T cells played a role as mediator cells in the first 72 h of renal IRI ( Hochegger et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

“…Observed an increase in CD4 memory T cells in patients who developed immune checkpoint inhibitor-related AKI ( Farooqui et al, 2023 ). Mast cells had potential protective effects on tissue remodeling post-injury ( van der Elst et al, 2023 ). These immune cells were differentially infiltrated in AKI, which could serve as a potential regulatory point for AKI treatment.…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of the diagnostic signature associated with immune microenvironment of acute kidney injury based on ferroptosis-related genes through integrated bioinformatics analysis and machine learning

Chen

Liu

et al. 2023

Front. Cell Dev. Biol.

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Background: Acute kidney injury (AKI) is a common and severe disease, which poses a global health burden with high morbidity and mortality. In recent years, ferroptosis has been recognized as being deeply related to Acute kidney injury. Our aim is to develop a diagnostic signature for Acute kidney injury based on ferroptosis-related genes (FRGs) through integrated bioinformatics analysis and machine learning.Methods: Our previously uploaded mouse Acute kidney injury dataset GSE192883 and another dataset, GSE153625, were downloaded to identify commonly expressed differentially expressed genes (coDEGs) through bioinformatic analysis. The FRGs were then overlapped with the coDEGs to identify differentially expressed FRGs (deFRGs). Immune cell infiltration was used to investigate immune cell dysregulation in Acute kidney injury. Functional enrichment analysis and protein-protein interaction network analysis were applied to identify candidate hub genes for Acute kidney injury. Then, receiver operator characteristic curve analysis and machine learning analysis (Lasso) were used to screen for diagnostic markers in two human datasets. Finally, these potential biomarkers were validated by quantitative real-time PCR in an Acute kidney injury model and across multiple datasets.Results: A total of 885 coDEGs and 33 deFRGs were commonly identified as differentially expressed in both GSE192883 and GSE153625 datasets. In cluster 1 of the coDEGs PPI network, we found a group of 20 genes clustered together with deFRGs, resulting in a total of 48 upregulated hub genes being identified. After ROC analysis, we discovered that 25 hub genes had an area under the curve (AUC) greater than 0.7; Lcn2, Plin2, and Atf3 all had AUCs over than this threshold in both human datasets GSE217427 and GSE139061. Through Lasso analysis, four hub genes (Lcn2, Atf3, Pir, and Mcm3) were screened for building a nomogram and evaluating diagnostic value. Finally, the expression of these four genes was validated in Acute kidney injury datasets and laboratory investigations, revealing that they may serve as ideal ferroptosis markers for Acute kidney injury.Conclusion: Four hub genes (Lcn2, Atf3, Pir, and Mcm3) were identified. After verification, the signature’s versatility was confirmed and a nomogram model based on these four genes effectively distinguished Acute kidney injury samples. Our findings provide critical insight into the progression of Acute kidney injury and can guide individualized diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification and validation of the diagnostic signature associated with immune microenvironment of acute kidney injury based on ferroptosis-related genes through integrated bioinformatics analysis and machine learning

Chen

Liu

et al. 2023

Front. Cell Dev. Biol.

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“…At this level, MCs have been shown to regulate inflammation, and both pro-and anti-inflammatory activity have been reported in diseased kidney [55,56]. Furthermore, MCs have been implicated in graft rejection [57], cancer progression [58], inflammatory bowel disease [59,60], atherosclerotic plaque progression [61], arthritis [62], osteoporosis [63], psoriasis [64][65][66][67], atopic [68,69] and allergic contact dermatitis [70][71][72].…”

Section: Role Of Mast Cells In Pathologymentioning

confidence: 99%

Mast Cell Activation Syndrome Update—A Dermatological Perspective

Mihele

Nistor

Bruma

et al. 2023

JPM

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Mast cells (MCs) are infamous for their role in potentially fatal anaphylaxis reactions. In the last two decades, a more complex picture has emerged, as it has become obvious that MCs are much more than just IgE effectors of anaphylaxis. MCs are defenders against a host of infectious and toxic aggressions (their interactions with other components of the immune system are not yet fully understood) and after the insult has ended, MCs continue to play a role in inflammation regulation and tissue repair. Unfortunately, MC involvement in pathology is also significant. Apart from their role in allergies, MCs can proliferate clonally to produce systemic mastocytosis. They have also been implicated in excessive fibrosis, keloid scaring, graft rejection and chronic inflammation, especially at the level of the skin and gut. In recent years, the term MC activation syndrome (MCAS) was proposed to account for symptoms caused by MC activation, and clear diagnostic criteria have been defined. However, not all authors agree with these criteria, as some find them too restrictive, potentially leaving much of the MC-related pathology unaccounted for. Here, we review the current knowledge on the physiological and pathological roles of MCs, with a dermatological emphasis, and discuss the MCAS classification.

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confidence: 99%

“…4,5 Research has shown that in the setting of acute KTx rejection, MCs are increased. 5,6 Additionally, in chronic transplant rejection there is also an increase in MCs number. [7][8][9] According to the Banff Classification for Allograft Pathology, the diagnosis "suspicious (borderline) for TCMR (bTCMR)" is currently defined as foci of tubulitis (t1 or greater) with mild interstitial inflammation (i1), or mild (t1) tubulitis with moderate-severe interstitial inflammation (i2 or i3).…”

mentioning

confidence: 99%

Mast Cells in Kidney Transplant Biopsies With Borderline T Cell-mediated Rejection and Their Relation to Chronicity

Varol

Elst

Baan

et al. 2023

Transplantation Direct

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Background. Mast cells are potential contributors to chronic changes in kidney transplants (KTx). Here, the role of mast cells (MCs) in KTx is investigated in patients with minimal inflammatory lesions. Methods. Fourty-seven KTx biopsies (2009–2018) with borderline pathological evidence for T cell-mediated rejection according to the Banff’17 Update were retrospectively included and corresponding clinical data was collected. Immunohistochemistry for tryptase was performed on formalin-fixed paraffin-embedded sections. Cortical MCs were counted and corrected for area (MC/mm²). Interstitial fibrosis was assessed by Sirius Red staining and quantified using digital image analysis (QuPath). Results. Increased MC number was correlated to donor age (spearman’s r = 0.35, P = 0.022), deceased donor kidneys (mean difference = 0.74, t [32.5] = 2.21, P = 0.035), and delayed graft function (MD = 0.78, t [33.9] = 2.43, P = 0.020). Increased MC number was also correlated to the amount of interstitial fibrosis (r = 0.42, P = 0.003) but did not correlate with transplant function over time (r = −0.14 , P = 0.36). Additionally, transplant survival 2 y post-biopsy was not correlated to MC number (mean difference = −0.02, t [15.36] = −0.06, P = 0.96). Conclusions. MC number in suspicious (borderline) for acute T cell-mediated rejection is correlated to interstitial fibrosis and time post-transplantation, suggesting MCs to be a marker for cumulative burden of tissue injury. There was no association between MCs and transplant function over time or transplant survival 2 y post-biopsy. It remains unclear whether MCs are just a bystander or have pro-inflammatory or anti-inflammatory effects in the KTx with minimal lesions.

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The mast cell: A Janus in kidney transplants

Cited by 3 publications

References 133 publications

Identification and validation of the diagnostic signature associated with immune microenvironment of acute kidney injury based on ferroptosis-related genes through integrated bioinformatics analysis and machine learning

Identification and validation of the diagnostic signature associated with immune microenvironment of acute kidney injury based on ferroptosis-related genes through integrated bioinformatics analysis and machine learning

Mast Cell Activation Syndrome Update—A Dermatological Perspective

Mast Cells in Kidney Transplant Biopsies With Borderline T Cell-mediated Rejection and Their Relation to Chronicity

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