EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells

Roy, Suyasha; Rizvi, Zaigham Abbas; Clarke, Adam J.; Macdonald, Felicity; Pandey, Abhaydeep; Zaiss, Dietmar M.; Simon, Anna Kathrina; Awasthi, Amit

doi:10.1038/s41467-021-23042-x

Cited by 42 publications

(44 citation statements)

References 64 publications

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“…The relative expression of each gene was expressed as fold change and was calculated by subtracting the cycling threshold (Ct) value of hypoxantine-guanine phosphoribosyltransferase (HGPRT-endogenous control gene) from the Ct value of the target gene (ΔCT). Fold change was then calculated according to the previously described formula POWER(2,-ΔCT)*10,000 (Malik et al, 2017;Rizvi et al, 2021;Roy et al, 2021). The list of the primers is provided as follows.…”

Section: Qpcrmentioning

confidence: 99%

Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

Rizvi

Dalal

Sadhu

et al. 2022

eLife

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Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in the Golden Syrian hamster causes lung pathology that resembles human coronavirus disease (COVID-19). However, extra-pulmonary pathologies associated with SARS-CoV-2 infection and post COVID sequelae remain to be understood. Here we show, using a hamster model, that the early phase of SARS-CoV-2 infection leads to an acute inflammatory response and lung pathologies, while the late phase of infection causes cardiovascular complications (CVC) characterized by ventricular wall thickening associated with increased ventricular mass/ body mass ratio and interstitial coronary fibrosis. Molecular profiling further substantiated our findings of CVC, as SARS-CoV-2-infected hamsters showed elevated levels of serum cardiac Troponin-I (cTnI), cholesterol, low-density lipoprotein and long-chain fatty acid triglycerides. Serum metabolomics profiling of SARS-CoV-2-infected hamsters identified N-acetylneuraminate, a functional metabolite found to be associated with CVC, as a metabolic marker was found to be common between SARS-CoV-2-infected hamsters and COVID-19 patients. Together, we propose hamsters as a suitable animal model to study post-COVID sequelae associated with CVC which could be extended to therapeutic interventions.

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Section: Qpcrmentioning

confidence: 99%

Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

Rizvi

Dalal

Sadhu

et al. 2022

eLife

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“…It reprograms the differentiation of Th2 cells and promotes an IL9–producing subset, Th9 cells [ 154 ]. In this case, EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing Th9 cells [ 155 ], and HDAC SIRT1 negatively regulates the differentiation of IL-9-producing CD4 + T cells [ 156 ]. Th9 cells can be generated by treatment of naive T cells with TGF-β and IL-4 in vitro.…”

Section: Epigenetic Regulation Of the Immune Cells And Immune-associated Moleculesmentioning

confidence: 99%

Epigenetic modulation of antitumor immunity for improved cancer immunotherapy

et al. 2021

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Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and functionality, and the immunogenicity of cancer cells. Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 and STING, are regulated via epigenetic mechanisms in immune or/and cancer cells, as are immune checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by immune cells and tumor-associated stromal cells. Thus, therapeutic strategies implementing epigenetic modulating drugs are expected to significantly impact the tumor microenvironment (TME) by promoting transcriptional and metabolic reprogramming in local immune cell populations, resulting in inhibition of immunosuppressive cells (MDSCs and Treg) and the activation of anti-tumor T effector cells, professional antigen presenting cells (APC), as well as cancer cells which can serve as non-professional APC. In the latter instance, epigenetic modulating agents may coordinately promote tumor immunogenicity by inducing de novo expression of transcriptionally repressed tumor-associated antigens, increasing expression of neoantigens and MHC processing/presentation machinery, and activating tumor immunogenic cell death (ICD). ICD provides a rich source of immunogens for anti-tumor T cell cross-priming and sensitizing cancer cells to interventional immunotherapy. In this way, epigenetic modulators may be envisioned as effective components in combination immunotherapy approaches capable of mediating superior therapeutic efficacy.

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“…The protein encoded by AREG is a member of the epidermal growth factor (EGF) family. As an EGFR ligand produced by Th9 cells, the study has shown that AREG can enhance Th9 cell differentiation [ 44 ]. Moreover, the AREG/EGFR signaling pathway may be involved in cancer progression through enhanced Treg cell function, leading to the activation of NFκB, which is closely related to neoadjuvant chemotherapy response and survival of patients with EAC [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a prognostic signature of patients with esophagus adenocarcinoma by using immune-related genes

Zhang

Liu

Kong³

et al. 2021

BMC Bioinformatics

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Background Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor prognosis. The immune-related genes (IRGs) are crucial to immunocytes tumor infiltration. This study aimed to construct a IRG-related prediction signature in EAC. Methods The related data of EAC patients and IRGs were obtained from the TCGA and ImmPort database, respectively. The cox regression analysis constructed the prediction signature and explored the transcription factors regulatory network through the Cistrome database. TIMER database and CIBERSORT analytical tool were utilized to explore the immunocytes infiltration analysis. Results The prediction signature with 12 IRGs (ADRM1, CXCL1, SEMG1, CCL26, CCL24, AREG, IL23A, UCN2, FGFR4, IL17RB, TNFRSF11A, and TNFRSF21) was constructed. Overall survival (OS) curves indicate that the survival rate of the high-risk group is significantly shorter than the low-risk group (P = 7.26e−07), and the AUC of 1-, 3- and 5- year survival prediction rates is 0.871, 0.924, and 0.961, respectively. Compared with traditional features, the ROC curve of the risk score in the EAC patients (0.967) is significant than T (0.57), N (0.738), M (0.568), and Stage (0.768). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are accurate by the combined analysis of the risk score, Sex, M stage, and Stage (The AUC of 1- and 3-years are 0.911, and 0.853). Conclusion The 12 prognosis-related IRGs might be promising therapeutic targets for EAC.

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EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells

Cited by 42 publications

References 64 publications

Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

Golden Syrian hamster as a model to study cardiovascular complications associated with SARS-CoV-2 infection

Epigenetic modulation of antitumor immunity for improved cancer immunotherapy

Development of a prognostic signature of patients with esophagus adenocarcinoma by using immune-related genes

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