Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages

Zou, Ziqi; Li, Mengyao; Zhou, Yunlian; Pan, Ting; Lai, Lihua; Wang, Qingqing; Zhang, Lining; Wang, Qun; Song, Yinjing; Zhang, Yuanyuan

doi:10.3389/fimmu.2021.642715

Cited by 8 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PPP1R15A is usually a target of ATF4 in endoplasmic reticulum stress [ 41 ]. TNF (tumor necrosis factor) encodes proinflammatory cytokines for the TNF family, which is primarily secreted by macrophages [ 42 , 43 ]. TNF is capable of regulating lipid metabolism, cell growth, protein binding, and cytokine activity [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Spatial Transcriptomic Analysis Using R-Based Computational Machine Learning Reveals the Genetic Profile of Yang or Yin Deficiency Syndrome in Chinese Medicine Theory

Zhang

Tam

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objectives. Yang and Yin are two main concepts responsible for harmonious balance reflecting health conditions based on Chinese medicine theory. Of note, deficiency of either Yang or Yin is associated with disease susceptibility. In this study, we aim to clarify the molecular feature of Yang and Yin deficiency by reanalyzing a transcriptomic data set retrieved from the GEO database using R-based machine learning analyses, which lays a foundation for medical diagnosis, prevention, and treatment of unbalanced Yang or Yin. Methods. Besides conventional methods for target mining, we took the advantage of spatial transcriptomic analysis using R-based machine learning approaches to elucidate molecular profiles of Yin and Yang deficiency by reanalyzing an RNA-Seq data set (GSE87474) in the GEO focusing on peripheral blood mononuclear cells (PBMCs). The add-on functions in R including GEOquery, DESeq2, WGCNA (target identification with a scale-free topological assumption), Scatterplot3d, Tidyverse, and UpsetR were used. For information in the selected GEO data set, PBMCs representing 20,740 expressed genes were collected from subjects with Yang or Yin deficiency (n = 12 each), based on Chinese medicine-related diagnostic criteria. Results. The symptomatic gene targets for Yang deficiency (KAT2B, NFKB2, CREBBP, GTF2H3) or Yin deficiency (JUNB, JUND, NGLY1, TNF, RAF1, PPP1R15A) were potentially discovered. CREBBP was identified as a shared key contributive gene regulating either the Yang or Yin deficiency group. The intrinsic molecular characteristics of these specific genes could link with clinical observations of Yang/Yin deficiency, in which Yang deficiency is associated with immune dysfunction tendency and energy deregulation, while Yin deficiency mainly contains oxidative stress, dysfunction of the immune system, and abnormal lipid/protein metabolism. Conclusion. Our study provides representative gene targets and modules for supporting clinical traits of Yang or Yin deficiency in Chinese medicine theory, which is beneficial for promoting the modernization of Chinese medicine theory. Besides, R-based machine learning approaches adopted in this study might be further applied for investigating the underlying genetic polymorphisms related to Chinese medicine theory.

show abstract

Section: Discussionmentioning

confidence: 99%

Spatial Transcriptomic Analysis Using R-Based Computational Machine Learning Reveals the Genetic Profile of Yang or Yin Deficiency Syndrome in Chinese Medicine Theory

Zhang

Tam

Tang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…TNF-α-induced protein 8-like 2 (TNFAIP8L2, TIPE2) is a newly discovered negative immunoregulatory domain that plays a vital role in regulating inflammatory and cellular immune responses, and is an essential negative regulator of both innate and adaptive immunity by maintaining immune homeostasis [267,268]. TIPE2 appeared to be a critical immunoregulatory molecule involved in the immunosuppressive function of CD4(+)CD25(+) T reg cells [269].…”

Section: Tnf-α-induced Protein 8-like 2 (Tnfaip8l2 Tipe2)mentioning

confidence: 99%

A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis

Vebr,

Pomahačová,

Sýkora

et al. 2023

Biomedicines

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a lifelong inflammatory immune mediated disorder, encompassing Crohn’s disease (CD) and ulcerative colitis (UC); however, the cause and specific pathogenesis of IBD is yet incompletely understood. Multiple cytokines produced by different immune cell types results in complex functional networks that constitute a highly regulated messaging network of signaling pathways. Applying biological mechanisms underlying IBD at the single omic level, technologies and genetic engineering enable the quantification of the pattern of released cytokines and new insights into the cytokine landscape of IBD. We focus on the existing literature dealing with the biology of pro- or anti-inflammatory cytokines and interactions that facilitate cell-based modulation of the immune system for IBD inflammation. We summarize the main roles of substantial cytokines in IBD related to homeostatic tissue functions and the remodeling of cytokine networks in IBD, which may be specifically valuable for successful cytokine-targeted therapies via marketed products. Cytokines and their receptors are validated targets for multiple therapeutic areas, we review the current strategies for therapeutic intervention and developing cytokine-targeted therapies. New biologics have shown efficacy in the last few decades for the management of IBD; unfortunately, many patients are nonresponsive or develop therapy resistance over time, creating a need for novel therapeutics. Thus, the treatment options for IBD beyond the immune-modifying anti-TNF agents or combination therapies are expanding rapidly. Further studies are needed to fully understand the immune response, networks of cytokines, and the direct pathogenetic relevance regarding individually tailored, safe and efficient targeted-biotherapeutics.

show abstract

“…Tumor necrosis factor- α -induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been reported to play an important role in regulating the function of macrophages [ 8 , 9 ]. Studies have also confirmed the role of TIPE2 in cancer and cell apoptosis [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Ameliorates Cardiac Hypertrophy by Targeting TLR4 in Macrophages

Yao

Kong

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), a novel immunoregulatory protein, has been reported to regulate inflammation and apoptosis. The role of TIPE2 in cardiovascular disease, especially cardiac hypertrophy, has not been elucidated. Thus, the aim of the present study was to explore the role of TIPE2 in cardiac hypertrophy. Methods. Mice were subjected to aortic banding (AB) to induce an adverse hypertrophic model. To overexpress TIPE2, mice were injected with a lentiviral vector expressing TIPE2. Echocardiographic and hemodynamic analyses were used to evaluate cardiac function. Neonatal rat cardiomyocytes (NRCMs) and mouse peritoneal macrophages (MPMs) were isolated and stimulated with angiotensin II. NRCMs and MPM were also cocultured and stimulated with angiotensin II. Cells were transfected with Lenti-TIPE2 to overexpress TIPE2. Results. TIPE2 expression levels were downregulated in hypertrophic mouse hearts and in macrophages in heart tissue. TIPE2 overexpression attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, we found that TIPE2 overexpression in neonatal cardiomyocytes did not relieve the angiotensin II-induced hypertrophic response in vitro. Furthermore, TIPE2 overexpression downregulated TLR4 and NF-κB signaling in macrophages but not in cardiomyocytes, which led to diminished inflammation in macrophages and consequently reduced the activation of hypertrophic Akt signaling in cardiomyocytes. TLR4 inhibition by TAK-242 did not enhance the antihypertrophic effect of TIPE2 overexpression. Conclusions. The present study indicated that TIPE2 represses macrophage activation by targeting TLR4, subsequently inhibiting cardiac hypertrophy.

show abstract

Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Negatively Regulates Innate Immunity Against RNA Virus by Targeting RIG-I in Macrophages

Cited by 8 publications

References 47 publications

Spatial Transcriptomic Analysis Using R-Based Computational Machine Learning Reveals the Genetic Profile of Yang or Yin Deficiency Syndrome in Chinese Medicine Theory

Spatial Transcriptomic Analysis Using R-Based Computational Machine Learning Reveals the Genetic Profile of Yang or Yin Deficiency Syndrome in Chinese Medicine Theory

A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis

Tumor Necrosis Factor-α-Induced Protein 8-Like 2 Ameliorates Cardiac Hypertrophy by Targeting TLR4 in Macrophages

Contact Info

Product

Resources

About