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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 15040

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Prof. Dr. Marcos López Hoyos

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1. Immunology Service, University Hospital Marqués de Valdecilla-IDIVAL, 39008 Santander, Spain
2. Molecular Biology Department, Universidad de Cantabria, 39005 Santander, Spain
Interests: immunology; autoimmunity; transplantation; tolerance; human pathology; biomarkers
Special Issues, Collections and Topics in MDPI journals

Dr. Jordi Ochando

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Instituto de Salud Carlos III, Majadahonda, 28029 Madrid, Spain
Interests: trained immunity; immune tolerance; organ transplantation

Special Issue Information

Dear Colleagues,

The immune system is a complex network of organs and cells that distinguishes between self and non-self. Its advanced degree of specialization allows for the immune system to recognize and neutralize self damage-associated molecular patterns (DAMPs) and non-self pathogen-associated molecular patterns (PAMPs). This is a tightly regulated system, and failure in the correct shutdown of the immune response may be the basis of many chronic inflammatory processes. Inflammation compromises immunological tolerance and may lead to the development of autoimmune diseases, and cause organ transplant rejection. In addition, the long-term responsiveness to pathogenic stimuli are associated with changes in the cellular energy metabolism towards aerobic glycolysis, which results in the secretion of inflammatory molecules during end-stage renal disease (ESRD) and chronic kidney disease (CKD). This Issue focuses in altered immune responses from the molecular level (microRNA, microbiota, etc.) to the cellular level (apoptosis, Tregs, auto/alloantibodies, MDSCs, etc.) in human and mouse models, which can result in the development of diagnostic and/or therapeutic approaches in kidney diseases and kidney transplantation.

Dr. Marcos Lopez-Hoyos
Dr. Jordi Ochando
Guest Editors

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Published Papers (5 papers)

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Research

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13 pages, 2115 KiB

Open AccessArticle

Immunological Pattern in IgA Nephropathy

by Clara Esteve Cols, Freddzia-Amanda Graterol Torres, Bibiana Quirant Sánchez, Helena Marco Rusiñol, Maruja Isabel Navarro Díaz, Jordi Ara del Rey and Eva Mª Martínez Cáceres

Int. J. Mol. Sci. 2020, 21(4), 1389; https://doi.org/10.3390/ijms21041389 - 18 Feb 2020

Cited by 14 | Viewed by 3206

Abstract

The current gold-standard diagnostic technique for IgA nephropathy (IgAN), the leading form of primary glomerulonephritis, is renal biopsy. CD89 (the main IgA receptor) is expressed on the surface of monocytes and plays a role in disease pathogenesis. Immunocomplexes formed by sCD89 (soluble form) and Gd-IgA1 are related to disease prognosis. We hypothesize that reduced CD89 surface expression on monocytes may be a marker of disease severity. We aimed to analyze leukocyte subpopulations in peripheral blood and CD89 surface expression on monocytes in a prospective study of 22 patients and 12 healthy subjects (HS). Leukocyte subpopulations and CD89 expression were analyzed by flow cytometry. IgAN patients had a higher percentage of activated and effector memory CD4⁺ and CD8⁺ T lymphocytes, a lower percentage of transitional B lymphocytes and plasmablasts, and a higher percentage of CD56^dimCD16⁺ NK cells and myeloid dendritic cells compared with HS. Correlations between reduced CD89 expression levels on nonclassical monocytes, histological findings of a poor prognosis on renal biopsy and baseline renal function were observed. IgAN patients show a characteristic immunological pattern in peripheral blood. A reduced expression level of CD89 on nonclassical monocytes identifies patients with a worse renal prognosis. Full article

(This article belongs to the Special Issue Renal Disease and Immunity)

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18 pages, 4919 KiB

Open AccessArticle

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection

by Juan Irure-Ventura, David San Segundo, Emilio Rodrigo, David Merino, Lara Belmar-Vega, Juan Carlos Ruiz San Millán, Rosalía Valero, Adalberto Benito and Marcos López-Hoyos

Int. J. Mol. Sci. 2020, 21(3), 779; https://doi.org/10.3390/ijms21030779 - 25 Jan 2020

Cited by 8 | Viewed by 2539

Abstract

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the effect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who suffered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR. Full article

(This article belongs to the Special Issue Renal Disease and Immunity)

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11 pages, 1701 KiB

Open AccessArticle

Exploring Frequencies of Circulating Specific Th17 Cells against Myeloperoxidase and Proteinase 3 in ANCA Associated Vasculitis

by Laura Martinez Valenzuela, Juliana Draibe, Maria Quero, Xavier Fulladosa, Josep Maria Cruzado, Oriol Bestard and Juan Torras

Int. J. Mol. Sci. 2019, 20(23), 5820; https://doi.org/10.3390/ijms20235820 - 20 Nov 2019

Cited by 6 | Viewed by 2255

Abstract

Background: The role of the T helper 17 (Th17) cell subset in anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is controversial. We hypothesized that a specific Th17 response to myeloperoxidase (MPO) or proteinase 3 (PR3) is detectable in AAV patients and is different among the disease phases. Methods: We analyzed 43 AAV patients with renal involvement (21 acute and 22 remission patients), and 12 healthy controls. Peripheral blood mononuclear cells (PBMCs) were cultured with PR3/MPO over 48 h. Thereafter, frequencies of MPO/PR3-specific Th17 cells were assessed using an enzyme-linked immunosorbent spot (ELISpot) assay. Supernatant IL-17 concentration was quantified using ELISA. Finally, specific Th17 response after depletion of T regulatory lymphocytes (T-regs) in some remission patients was compared to the non T-reg-depleted response. Results: Specific Th17 cell number was higher in acute patients compared to remission (p = 0.004). Specific Th17 cell number performed well in the disease activity detection (ROC curve area under the curve (AUC) = 0.87; p = 0.0001) with an optimal cut-off of 6 spots/million. Patients above this cut-off showed higher serum creatinine (p = 0.004), C-reactive protein (CRP) (p = 0.001) and ANCA titer (p = 0.032). Supernatant IL-17 concentration was higher in acute patients compared to remission (p = 0.035) and did not normalize to healthy control levels (p = 0.01). Conclusions: A specific Th17 cell response is present in AAV patients. This response is more pronounced in the acute phase, but persists in remission. Full article

(This article belongs to the Special Issue Renal Disease and Immunity)

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Review

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13 pages, 591 KiB

Open AccessReview

Transcriptome Analysis in Renal Transplant Biopsies Not Fulfilling Rejection Criteria

by Francesc Moreso, Joana Sellarès, María José Soler and Daniel Serón

Int. J. Mol. Sci. 2020, 21(6), 2245; https://doi.org/10.3390/ijms21062245 - 24 Mar 2020

Cited by 3 | Viewed by 2769

Abstract

The clinical significance of renal transplant biopsies displaying borderline changes suspicious for T-cell mediated rejection (TCMR) or interstitial fibrosis and tubular atrophy (IFTA) with interstitial inflammation has not been well defined. Molecular profiling to evaluate renal transplant biopsies using microarrays has been shown to be an objective measurement that adds precision to conventional histology. We review the contribution of transcriptomic analysis in surveillance and indication biopsies with borderline changes and IFTA associated with variable degrees of inflammation. Transcriptome analysis applied to biopsies with borderline changes allows to distinguish patients with rejection from those in whom mild inflammation mainly represents a response to injury. Biopsies with IFTA and inflammation occurring in unscarred tissue display a molecular pattern similar to TCMR while biopsies with IFTA and inflammation in scarred tissue, apart from T-cell activation, also express B cell, immunoglobulin and mast cell-related genes. Additionally, patients at risk for IFTA progression can be identified by genes mainly reflecting fibroblast dysregulation and immune activation. At present, it is not well established whether the expression of rejection gene transcripts in patients with fibrosis and inflammation is the consequence of an alloimmune response, tissue damage or a combination of both. Full article

(This article belongs to the Special Issue Renal Disease and Immunity)

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15 pages, 1103 KiB

Open AccessReview

Emerging Roles of Interleukin-33-responsive Kidney Group 2 Innate Lymphoid Cells in Acute Kidney Injury

by Wei-Yu Chen, Lung-Chih Li, Yi-Hsiu Wu, Jenq-Lin Yang and Hong-Tai Tzeng

Int. J. Mol. Sci. 2020, 21(4), 1544; https://doi.org/10.3390/ijms21041544 - 24 Feb 2020

Cited by 5 | Viewed by 3778

Abstract

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses. IL-33 triggers pleiotropic immune functions in multiple types of immune cells, which express the IL-33 receptor, ST2. Recent studies have revealed the potential applications of IL-33 for treating acute kidney injury in preclinical animal models. However, IL-33 and IL-33-responding immune cells are reported to exhibit both detrimental and beneficial roles. The IL-33-mediated immunomodulatory functions have been investigated using loss-of-function approaches, such as IL33-deficient mice, IL-33 antagonists, or administration of exogenous IL-33 recombinant protein. This review will discuss the key findings on IL-33-mediated activation of kidney resident group 2 innate lymphoid cells (ILC2s) and summarize the current understanding of the differential functions of endogenous IL-33 and exogenous IL-33 and their potential implications in treating acute kidney injury. Full article

(This article belongs to the Special Issue Renal Disease and Immunity)

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