Treg Cells: A LAGging Hand Holds the Double-Edged Sword of the IL-23 Axis

Rankin, Lucille C.; Arpaia, Nicholas

doi:10.1016/j.immuni.2018.08.008

Cited by 9 publications

(4 citation statements)

References 9 publications

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“…An interplay between ILC3 and Treg has been reported, especially in the gut and intestine, with ILC3s interacting with microbiota-specific regulatory T cells to establish tolerance in the gut 47. Noteworthy, an interplay between ILC3 and LAG+ Tregs has also been reported in the context of gut inflammation 48 49. Thus, our results are in line with these observations, with an ILC3 dysregulation being associated with disease type/localisation in AD and AIF.…”

Section: Discussionsupporting

confidence: 90%

Deep immunophenotyping reveals that autoimmune and autoinflammatory disorders are spread along two immunological axes capturing disease inflammation levels and types

Tchitchek,

Binvignat,

Roux

et al. 2024

Annals of the Rheumatic Diseases

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ObjectivesBased on genetic associations, McGonagle and McDermott suggested a classification of autoimmune and autoinflammatory diseases as a continuum ranging from purely autoimmune to purely autoinflammatory diseases and comprising diseases with both components. We used deep immunophenotyping to identify immune cell populations and molecular targets characterising this continuum.MethodsWe collected blood from 443 patients with one of 15 autoimmune or autoinflammatory diseases and 71 healthy volunteers. Deep phenotyping was performed using 13 flow cytometry panels characterising over 600 innate and adaptive cell populations. Unsupervised and supervised analyses were conducted to identify disease clusters with their common and specific cell parameters.ResultsUnsupervised clustering categorised these diseases into five clusters. Principal component analysis deconvoluted this clustering into two immunological axes. The first axis was driven by the ratio of LAG3+ to ICOS+ in regulatory T lymphocytes (Tregs), and segregated diseases based on their inflammation levels. The second axis was driven by activated Tregs and type 3 innate lymphoid cells (ILC3s), and segregated diseases based on their types of affected tissues. We identified a signature of 23 cell populations that accurately characterised the five disease clusters.ConclusionsWe have refined the monodimensional continuum of autoimmune and autoinflammatory diseases as a continuum characterised by both disease inflammation levels and targeted tissues. Such classification should be helpful for defining therapies. Our results call for further investigations into the role of the LAG3+/ICOS+ balance in Tregs and the contribution of ILC3s in autoimmune and autoinflammatory diseases.Trial registration numberNCT02466217.

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Section: Discussionsupporting

confidence: 90%

Deep immunophenotyping reveals that autoimmune and autoinflammatory disorders are spread along two immunological axes capturing disease inflammation levels and types

Tchitchek,

Binvignat,

Roux

et al. 2024

Annals of the Rheumatic Diseases

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“…Many of the genes are found to play different roles through different mechanisms in different cancers. [53][54][55][56] Similarly, Siglec-15 has variable prognostic significance in diverse cancers, and even in different subtypes of the same cancer. It is well accepted that tumor heterogeneity is a major challenge in cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis

Zhang

Wang

et al. 2020

OncoImmunology

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Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is considered a novel anti-tumor target comparable to programmed cell death 1 ligand 1(PD-L1). However, little is known about Siglec-15. Our study aims to understand its expression signature, prognosis value, immune infiltration pattern, and biological function using multi-omic bioinformatics from public databases and verify them in lung cancer patients. Integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals showed Siglec-15 was overexpressed across cancers. Genetic and epigenetic alteration analysis was performed using cBioportal and UALCAN, showed Siglec-15 was regulated at the genetic and epigenetic levels. Survival estimated using Kaplan-Meier plotter indicated high Siglec-15 expression correlated with favorable or unfavorable outcomes depending on the different type and subtype of cancer. Components of immune microenvironment were analyzed using CIBERSORT, and the correlation between immune cells and Siglec-15 was found to be distinct across cancer types. Based on Gene Set Enrichment Analysis, Siglec-15 was implicated in pathways involved in immunity, metabolism, cancer, and infectious diseases. Lung cancer patients with positive Siglec-15 expression showed significantly short survival rates in progressionfree survival concomitant with reduced infiltration of CD20 + B, and dendritic cells by immunohistochemistry. Quantitative real-time PCR results indicated the overexpression of Siglec-15 was correlated with activation of the chemokine signaling pathway. In conclusion, Siglec-15 could serve as a vital prognostic biomarker and play an immune-regulatory role in tumors. These results provide us with clues to better understand Siglec-15 from the perspective of bioinformatics and highlight the importance of Siglec-15 in many types of cancer.

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“…Oncomine results were largely consistent with the results of these analyses. Many genes play different roles in different cancers (58)(59)(60), thus explaining the variable prognostic significance of ASF1B observed among cancer types and subtypes. Such tumor heterogeneity is a significant barrier to reliable tumor treatment [61][62][63].…”

Section: Discussionmentioning

confidence: 99%

ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types

et al. 2021

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Anti-silencing function 1B histone chaperone (ASF1B) is known to be an important modulator of oncogenic processes, yet its role in lung adenocarcinoma (LUAD) remains to be defined. In this study, an integrated assessment of The Cancer Genome Atlas (TCGA) and genotype-tissue expression (GTEx) datasets revealed the overexpression of ASF1B in all analyzed cancer types other than LAML. Genetic, epigenetic, microsatellite instability (MSI), and tumor mutational burden (TMB) analysis showed that ASF1B was regulated by single or multiple factors. Kaplan-Meier survival curves suggested that elevated ASF1B expression was associated with better or worse survival in a cancer type-dependent manner. The CIBERSORT algorithm was used to evaluate immune microenvironment composition, and distinct correlations between ASF1B expression and immune cell infiltration were evident when comparing tumor and normal tissue samples. Gene set enrichment analysis (GSEA) indicated that ASF1B was associated with proliferation- and immunity-related pathways. Knocking down ASF1B impaired the proliferation, affected cell cycle distribution, and induced cell apoptosis in LUAD cell lines. In contrast, ASF1B overexpression had no impact on the malignant characteristics of LUAD cells. At the mechanistic level, ASF1B served as an indirect regulator of DNA Polymerase Epsilon 3, Accessory Subunit (POLE3), CDC28 protein kinase regulatory subunit 1(CKS1B), Dihydrofolate reductase (DHFR), as established through proteomic profiling and Immunoprecipitation-Mass Spectrometry (IP-MS) analyses. Overall, these data suggested that ASF1B serves as a tumor promoter and potential target for cancer therapy and provided us with clues to better understand the importance of ASF1B in many types of cancer.

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Treg Cells: A LAGging Hand Holds the Double-Edged Sword of the IL-23 Axis

Cited by 9 publications

References 9 publications

Deep immunophenotyping reveals that autoimmune and autoinflammatory disorders are spread along two immunological axes capturing disease inflammation levels and types

Deep immunophenotyping reveals that autoimmune and autoinflammatory disorders are spread along two immunological axes capturing disease inflammation levels and types

Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis

ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types

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