CXCR5+PD1+ICOS+ Circulating T Follicular Helpers Are Associated With de novo Donor-Specific Antibodies After Renal Transplantation

Danger, Richard; Chesneau, Mélanie; Delbos, Florent; Bot, Sabine Le; Kerleau, Clarisse; Chenouard, Alexis; Ville, Simon; Degauque, Nicolas; Conchon, Sophie; Cesbron, Anne; Giral, Magali; Brouard, Sophie

doi:10.3389/fimmu.2019.02071

Cited by 30 publications

(32 citation statements)

References 43 publications

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“…DSA has been associated withboth acute and chronic rejection in solid organ allografts, and DSA is one of the major causes of chronic rejection in solid organ transplantation 39,40 . The roles of blood circulating CXCR5 + ICOS + CD4 + T cells in de novo DSA antibody responses has been reported in renal allograft recipients 41 . Another study also reported that PD-L1 expressed on Bregs can also suppress antibody responses 30 , but the mechanisms for the Breg PD-L1-mediated suppression of antibody response remain to be fully investigated.…”

Section: Discussionmentioning

confidence: 99%

Implication of TIGIT+ human memory B cells in immune regulation

et al. 2021

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Regulatory B cells (Bregs) contribute to immune regulation. However, the mechanisms of action of Bregs remain elusive. Here, we report that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells especially CD19+CD24hiCD27+CD39hiIgD−IgM+CD1c+ B cells is essential for effective immune regulation. Mechanistically, TIGIT on memory B cells controls immune response by directly acting on T cells and by arresting proinflammatory function of dendritic cells, resulting in the suppression of Th1, Th2, Th17, and CXCR5+ICOS+ T cell response while promoting immune regulatory function of T cells. TIGIT+ memory B cells are also superior to other B cells at expressing additional inhibitory molecules, including IL-10, TGFβ1, granzyme B, PD-L1, CD39/CD73, and TIM-1. Lack or decrease of TIGIT+ memory B cells is associated with increased donor-specific antibody and TFH response, and decreased Treg response in renal and liver allograft patients. Therefore, TIGIT+ human memory B cells play critical roles in immune regulation.

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Section: Discussionmentioning

confidence: 99%

Implication of TIGIT+ human memory B cells in immune regulation

et al. 2021

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“…ICOS is essential for Tfh development and plays important roles in B‐cells maturation and activation by combining ICOS‐L expressed on B cells [43]. Circulating ICOS+PD‐1+Tfh cells had been reported to play important roles in several diseases [44, 45]. In addition, our results also showed that the proliferation indicator Ki‐67 was higher in AAV patients, suggesting that Tfh cells are much more active in MPA patients, although the level of Tfh cells is not elevated.…”

Section: Discussionmentioning

confidence: 60%

Altered follicular regulatory T (Tfr)‐ and helper T (Tfh)‐cell subsets are associated with autoantibody levels in microscopic polyangiitis patients

Long

Feng

et al. 2021

Eur J Immunol

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Antineutrophil cytoplasmic antibodies (ANCA)‐associated vasculitis (AAV) is an autoimmune disease characterized by B cells‐derived ANCAs, and ANCA was proved to be a key factor in its pathogenesis. Follicular regulatory T (Tfr) and follicular helper T (Tfh) cells were T‐cell subsets that play important roles in B‐cell maturation and antibody production. However, their significances in microscopic polyangiitis (MPA) patients, one type of AAV, has not been thoroughly studied. In this study, comprehensive pattern analyses of circulating Tfr and Tfh were performed in MPA patients and healthy controls (HCs), and we found Tfr levels and Tfr/Tfh ratios were significantly decreased in MPA patients. Compared with HCs, Helios+, CD45RA‐FoxP3hi, and Ki‐67+ Tfr were lower in MPA patients, while CD226+ Tfr cells were higher. These phenotypes suggest that function and proliferation ability of Tfr cells were relatively impaired. Tfh subsets, including ICOS+PD‐1+ and Ki‐67+ Tfh, were significantly increased, suggesting that the function of Tfh was enhanced in MPA although the total Tfh levels did not change significantly. Circulating memory B cells and plasmablasts were significantly elevated and negatively correlated with Tfr levels and Tfr/Tfh ratios in MPA patients. In addition, Tfr levels and Tfr/Tfh ratios were negatively while Tfh was positively correlated with serum myeloperoxidase (MPO)‐ANCA levels. Furthermore, Tfr and Tfr/Tfh ratio were also reversely associated with SCr, BUN, IL‐4, and IL‐21 levels. Our results suggest that the imbalance of Tfr and Tfh functional subsets is related to increased level of autoantibodies in MPA patients, and we propose a new mechanism for the pathogenesis of MPA.

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“…The FaDA application allows users to profit from various data visualization options given a glance of data analysis, identifying significant findings and possibly highlighting outliers with limited time consumption. We have used two cases study from previously published datasets (16,18) to exhibit the usefulness of FaDA for common data generated from non-computational researchers; that entails microarray and flow cytometry. Note that despite FaDA proposal of various statistical options, it cannot replace recommendations from a statistician that users may need for particular cases as for any analysis software.…”

Section: Discussionmentioning

confidence: 99%

FaDA: A Shiny web application to accelerate common lab data analyses

Feseha

Moiteaux

Geffard

et al. 2020

Preprint

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Background-Web-based data analysis and visualization tools are mostly designed for specific purposes, such as data from whole transcriptome RNA sequencing or single-cell RNA sequencing. However, limited efforts have been made to develop tools designed for data of common laboratory data for non-computational scientists. The importance of such web-based tool is stressed by the current increased samples capacity of conventional laboratory tools such as quantitative PCR, flow cytometry or ELISA. Results-We provide a web-based application FaDA, developed with the R Shiny package providing users to perform statistical group comparisons, including parametric and nonparametric tests, with multiple testing corrections suitable for most of the standard wet-lab analyses. FaDA provides data visualization such as heatmap, principal component analysis (PCA) and receiver operating curve (ROC). Calculations are performed through the R language.Conclusions-FaDA application provides a free and intuitive interface allowing biologists without bioinformatic skills to easily and quickly perform common lab data analyses. The application is freely accessible at https://shiny-bird.univ-nantes.fr/app/Fada

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CXCR5+PD1+ICOS+ Circulating T Follicular Helpers Are Associated With de novo Donor-Specific Antibodies After Renal Transplantation

Cited by 30 publications

References 43 publications

Implication of TIGIT+ human memory B cells in immune regulation

Implication of TIGIT+ human memory B cells in immune regulation

Altered follicular regulatory T (Tfr)‐ and helper T (Tfh)‐cell subsets are associated with autoantibody levels in microscopic polyangiitis patients

FaDA: A Shiny web application to accelerate common lab data analyses

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