TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response

Chen, Jianwen; He, Ruirui; Sun, Wanwei; Gao, Ru; Peng, Qianwen; Zhu, Liwen; Du, Yanyun; Ma, Xiaojian; Guo, Xiaoli; Zhang, Huazhi; Tan, Chibing; Wang, Junhan; Zhang, Wei; Weng, Xiufang; Man, Jianghong; Bauer, Hermann; Wang, Qing Kenneth; Martin, Bradley N.; Zhang, Cunjin; Li, Xiaoxia; Wang, Chenhui

doi:10.1038/s41467-020-15564-7

Cited by 29 publications

(34 citation statements)

References 54 publications

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“…2c). rs654690, associated with psoriasis, IBD, and RA, falls page 10 of 58 preferentially in the accessible chromatin of Tregs and contacts the TAGAP promoter ~50kb downstream 23 ; TAGAP is a gene that has been shown to play a role in Th17 cell differentiation and thymocyte trafficking [24][25][26] (Fig. 3a).…”

Section: Resultsmentioning

confidence: 99%

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells

Mouri

Guo

Boer

et al. 2021

Preprint

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Genome-wide association studies have uncovered hundreds of autoimmune disease-associated loci; however, the causal genetic variant(s) within each locus are mostly unknown. Here, we perform high-throughput allele-specific reporter assays to prioritize disease-associated variants for five autoimmune diseases. By examining variants that both promote allele-specific reporter expression and are located in accessible chromatin, we identify 60 putatively causal variants that enrich for statistically fine-mapped variants by up to 57.8-fold. We introduced the risk allele of a prioritized variant (rs72928038) into a human T cell line and deleted the orthologous sequence in mice, both resulting in reduced BACH2 expression. Naive CD8 T cells from mice containing the deletion had reduced expression of genes that suppress activation and maintain stemness. Our results represent an example of an effective approach for prioritizing variants and studying their physiologically relevant effects.

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Section: Resultsmentioning

confidence: 99%

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells

Mouri

Guo

Boer

et al. 2021

Preprint

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“…IDO inhibitors can be used as immunometabolic adjuvants which safely and potently facilitate the e cacy of immunotherapy [22]. T-cell activation Rho GTPase-activating protein (TAGAP) is a GAP-domain containing protein, and was found to exert a role in T-cell differentiation [23]. ZHAO et al reported that the expression level of TAGAP was related to the positive number of lymph nodes in the prostate cancer [23].…”

Section: Discussionmentioning

confidence: 99%

“…T-cell activation Rho GTPase-activating protein (TAGAP) is a GAP-domain containing protein, and was found to exert a role in T-cell differentiation [23]. ZHAO et al reported that the expression level of TAGAP was related to the positive number of lymph nodes in the prostate cancer [23]. Perforin 1 (PRF1) encodes a protein with structural similarities to complement component C9 that is important in immunity.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Risk Model for Advanced Renal Cell Carcinoma (RCC) with Immune-Related Genes

Cao¹,

Zhang²,

Sun³

et al. 2020

Preprint

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BackgroundRenal cell carcinoma (RCC) is a common tumor of the urinary system. Nowadays, Immunotherapy is a hot topic in the treatment of solid tumors, especially for those tumors with pre-activated immune state.MethodsIn this study, we downloaded genomic and clinical data of RCC samples from The Cancer Genome Atlas database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. We selected the most relevant genes from each signature to construct a prognostic risk model to predict prognosis via Kaplan-Meier (KM) survival analysis. And the subgroups of the TCGA samples and external data from International Cancer Genome Consortium database were used to verify predictive stability of the model. We performed landscape analysis to assess the difference of gene mutant based on the data from TCGA. Finally, we explored the correlation between the selected genes and the level of tumor immune infiltration via Tumor Immune Estimation Resource (TIMER) platform.ResultsWe found that the four prognostic risk models constructed by the signatures all could divide the RCC samples into high- and low-risk groups with significantly different prognosis, especially in advanced RCC. And the prognostic risk model was constructed by 8 candidate genes (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) which divided the advanced RCC samples from TCGA database into high-risk and low-risk groups. And there was a significant difference in overall survival (OS) between the two groups. The validity of the model was verified by independent data from ICGC database. And the classification efficiency of the model was stable for the samples from different subgroups. landscape analysis showed that mutation ratios of some genes were different between two risk groups. In addition, the expression levels of the selected genes were significantly correlated with the infiltration degree of immune cells in the advanced RCC.ConclusionsSum up, eight immune-related genes were screened in our study to construct prognostic risk model with great predictive value for the prognosis of advanced RCC, and the genes were associated with infiltrating immune cells in tumors which have potential to conduct personalized treatment for advanced RCC.

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“…T-cell activation Rho GTPaseactivating protein (TAGAP) is a GAP-domain containing protein and was found to exert a role in T-cell differentiation [27]. ZHAO et al reported that the expression level of TAGAP was related to the positive number of lymph nodes in prostate cancer [27]. Perforin 1 (PRF1) encodes a protein with structural similarities to complement component C9 that is important in immunity.…”

Section: Discussionmentioning

confidence: 99%

“…IDO inhibitors can be used as immune-metabolic adjuvants which safely and potently facilitate the e cacy of immunotherapy [26]. T-cell activation Rho GTPaseactivating protein (TAGAP) is a GAP-domain containing protein and was found to exert a role in T-cell differentiation [27]. ZHAO et al reported that the expression level of TAGAP was related to the positive number of lymph nodes in prostate cancer [27].…”

Section: Discussionmentioning

confidence: 99%

A promising prognostic risk model for advanced renal cell carcinoma (RCC) with immune-related genes

Cao

Zhang

Sun

et al. 2020

Preprint

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Background Renal cell carcinoma (RCC) is a common tumor of the urinary system. Nowadays, immunotherapy is a hot topic in treatment of solid tumors, especially those with pre-activated immune state. Methods In this study, we have downloaded genomic and clinical data of RCC samples from TCGA database. Four immune-related genetic signatures were used to predict the prognosis of RCC by Cox regression analysis. We have established a prognostic risk model. The model consists of the genes most related to prognosis from the four genes signatures and aims at prognosis of the RCC samples via Kaplan-Meier survival analysis. Independent data from the ICGC database were used to test the predictive stability of the model. Furthermore, we have performed landscape analysis to assess the presence of mutations in the genes of interest in the RCC samples from the TCGA. Finally, we have explored the correlation between the selected genes and the level of tumor immune infiltration via TIMER platform. Results We have used four genetic signatures to construct prognostic risk models and found that each of the models divide the RCC samples into high- and low-risk groups, each of the groups correlating with significantly different prognosis, especially in the advanced RCC cases. A comprehensive prognostic risk model was constructed with eight candidate genes from four signatures (HLA-B, HLA-A, HLA-DRA, IDO1, TAGAP, CIITA, PRF1 and CD8B) dividing the advanced RCC samples from the TCGA database into high-risk and low-risk groups with a significant difference in the overall survival. The stability of the model was verified by independent data from the ICGC database. The samples from different subgroups. Landscape analysis showed that the mutation ratios in some genes were different between two risk groups. Besides, the expression levels of the selected genes were interrelated with the infiltration degree of the immune cells in the advanced RCC. ConclusionsEight immune-related genes were screened in our study to construct a promising prognostic risk model with a great predictive value for the prognosis of advanced RCC. The selected genes were associated with infiltrating immune cells in tumors which presents a chance for personalized treatment for advanced RCC.

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TAGAP instructs Th17 differentiation by bridging Dectin activation to EPHB2 signaling in innate antifungal response

Cited by 29 publications

References 54 publications

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells

Prioritization of autoimmune disease-associated genetic variants that perturb regulatory element activity in T cells

Prognostic Risk Model for Advanced Renal Cell Carcinoma (RCC) with Immune-Related Genes

A promising prognostic risk model for advanced renal cell carcinoma (RCC) with immune-related genes

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