Identification of<i>Acvr2a</i>as a Th17 Cell-Specific Gene Induced during Th17 Differentiation

Ihn, Hyun-Ju; Kim, Dong Hyeok; Oh, Sang-Ho; Moon, Chul Woo; Chung, Jin Woong; Song, Han-Jung; Kim, Kwang Dong

doi:10.1271/bbb.110436

Cited by 9 publications

(7 citation statements)

References 26 publications

(24 reference statements)

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“…The AVCR2A gene is a Th17-specific gene, and TGF-β (transforming growth factor-β) and IL-6 (interleukin 6) are required for the induction of ACVR2A [ 30 ]. Several studies have demonstrated that serum IL-6 levels are a diagnostic and prognostic biomarker for sepsis patients [ 31 – 33 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

Wang

Zhang

et al. 2014

Clinical Science

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The goal of the present study was to identify novel protein biomarkers from the target genes of six serum miRNAs that we identified previously in patients with sepsis. The target genes were predicted by bioinformatics analysis; the levels of the respective proteins in the sera of patients with sepsis were detected by ELISA. ACVR2A (activin A receptor, type IIA), FOXO1 (forkhead box O1), IHH (Indian hedgehog), STK4 (serine/threonine kinase 4) and DUSP3 (dual specificity phosphatase 3) were predicted to be the targets of the six miRNAs, and their encoded proteins were used for biomarker identification. Levels of ACVR2A (P<0.01) and FOXO1 (P<0.01) were significantly different among normal controls, patients with sepsis, patients with severe sepsis and patients with septic shock. Furthermore, levels of ACVR2A (P=0.025), FOXO1 (P<0.001), IHH (P=0.001) and STK4 (P=0.001) were differentially expressed in survivors and non-survivors. DUSP3 levels were not significantly different between any groups. Conjoin analysis of the four differentially expressed proteins showed that the area under the curve of the predictive probabilities was 0.875 [95% CI (confidence interval): 0.785–0.965], which was higher than the SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores. When the value of predictive probabilities was 0.449, the four proteins yielded a sensitivity of 68% and a specificity of 91%. Dynamic changes in ACVR2A, FOXO1 and IHH levels showed differential expression between survivors and non-survivors at all time points. On the basis of a combined analysis of the four identified proteins, their predictive value of 28-day mortality of patients with sepsis was better than the SOFA or APACHE II scores.

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Section: Discussionmentioning

confidence: 99%

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

Wang

Zhang

et al. 2014

Clinical Science

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“…3B). The enhancement of Treg cell-suppressive function by ACVR2A inhibition and its reported role in enhancing Th17 differentiation and function (29) suggested that ACVR2A regulates the balance between Treg and Th17 cells. Although not different in all donor pools tested (two out of three showed an effect), the enhancement of suppression by IGF1R inhibitor further validated our observation of the negative correlation of this receptor in Treg cell suppression (Fig.…”

Section: Validation For Genes Predicted From the Suppression Index Rementioning

confidence: 99%

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Hua

Davis

Hill

et al. 2015

The Journal of Immunology

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Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses. In this study, we analyzed human Treg cell subpopulations in the peripheral blood by performing genome-wide expression profiling of 40 Treg cell subsets from healthy donors. We found that the human peripheral blood Treg cell population is comprised of five major genomic subgroups, represented by 16 tractable subsets with a particular cell surface phenotype. These subsets possess a range of suppressive function and cytokine secretion and can exert a genomic footprint on target effector T (Teff) cells. Correlation analysis of variability in gene expression in the subsets identified several cell surface molecules associated with Treg suppressive function, and pharmacological interrogation revealed a set of genes having causative effect. The five genomic subgroups of Treg cells imposed a preserved pattern of gene expression on Teff cells, with a varying degree of genes being suppressed or induced. Notably, there was a cluster of genes induced by Treg cells that bolstered an autoinhibitory effect in Teff cells, and this induction appears to be governed by a different set of genes than ones involved in counteracting Teff activation. Our work shows an example of exploiting the diversity within human Treg cell subpopulations to dissect Treg cell biology.

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“…Expression of ACVR2A is required for the differentiation of T cells and specific only for CD4 + Th17 cell types. IL-17 secreted by Th17 cell types and is a key pro-inflammatory molecule associated with autoimmune diseases such as rheumatoid arthritis, IBD etc 38 . It highlights a common Th17 mediated pathogenesis mechanism for autoimmune gastrointestinal diseases, such as IBD and CD.…”

Section: Discussionmentioning

confidence: 99%

Association study identified biologically relevant receptor genes with synergistic functions in celiac disease

Banerjee

Bhagavatula

Sood

et al. 2019

Sci Rep

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Receptors are essential mediators of cellular physiology, which facilitate molecular and cellular cross-talk with the environment. Nearly 20% of the all known celiac disease (CD) genes are receptors by function. We hypothesized that novel biologically relevant susceptibility receptor genes act in synergy in CD pathogenesis. We attempted to identify novel receptor genes in CD by re-analyzing published Illumina Immunochip dense genotype data for a north Indian and a European (Dutch) cohort. North Indian dataset was screened for 269 known receptor genes. Association statistics for SNPs were considered with minor allele frequency >15% and association P ≤ 0.005 to attend desired study power. Identified markers were tested for cross-ethnic replication in a European CD dataset. Markers were analyzed in-silico to explain their functional significance in CD. Six novel SNPs from MOG (rs29231, p = 1.21e-11), GABBR1 (rs3025643, p = 1.60e-7), OR2H2 (rs1233388, p = 0.0002), ABCF1 (rs9262119, p = 0.0005), ADRA1A (rs10102024, p = 0.003), and ACVR2A (rs7560426, p = 0.004) were identified in north Indians, of which three genes namely, GABBR1 (rs3025643, p = 5.38e-8), OR2H2 (rs1233388, p = 3.29e-5) and ABCF1 (rs9262119, p = 0.0002) were replicated in Dutch. Tissue specific functional annotation, potential epigenetic regulation, co-expression, protein-protein interaction and pathway enrichment analyses indicated differential expression and synergistic function of key genes that could alter cellular homeostasis, ubiquitination mediated phagosome pathway and cellular protein processing to contribute for CD. At present multiple therapeutic compounds/drugs are available targeting GABBR1 and ADRA1A, which could be tested for their effectiveness against CD in controlled drug trials.

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Identification ofAcvr2aas a Th17 Cell-Specific Gene Induced during Th17 Differentiation

Cited by 9 publications

References 26 publications

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

Identification of four novel serum protein biomarkers in sepsis patients encoded by target genes of sepsis-related miRNAs

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Association study identified biologically relevant receptor genes with synergistic functions in celiac disease

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