The emerging role of histone deacetylase 1 in allergic diseases

Wang, Yongfang; Wang, Huiying

doi:10.3389/fimmu.2022.1027403

Cited by 7 publications

(8 citation statements)

References 93 publications

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“…Histone deacetylase 1 (HDAC1) is a member of class I HDACs, and plays an important role in adapting to external stimuli, including stress and allergens [39]. Given that Th2 cells are a major cause of allergic disorders, we anticipated that HDACs would play a part in controlling the synthesis of IL-4 and IL-13.…”

Section: Resultsmentioning

confidence: 99%

“…Inhibition of HDACs resulted in an up-regulated IL-13 production, while the presence of calcitriol affected the recruitment of HDAC1 in Th2 cells. Histone deacetylase 1 (HDAC1) is a member of class I HDACs, and plays an important role in adapting to external stimuli, including stress and allergens [39]. Given that Th2 cells are a major cause of allergic disorders, we anticipated that HDACs would play a part in controlling the synthesis of IL-4 and IL-13.…”

Section: Name Of the Primersmentioning

confidence: 99%

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Calcitriol impairs the secretion of IL-4 and IL-13 in Th2 cells via modulating VDR-Gata3-Gfi1 axis

Biswas,

Chattopadhyay,

Hazra

et al. 2023

Preprint

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The bioactive form of vitamin D, calcitriol exerts its biological function by binding to its cognate receptor VDR. Although calcitriol increased the expression of VDR in murine Th2 cells, IL-4 and IL-13 secretion were diminished significantly. Interestingly, IL-10 secretion increased post calcitriol treatment. The expression of Th2 master regulator Gata3 was attenuated by calcitriol. However, the expression of Gfi1, a transcriptional repressor, that prevents activated CD4+ T cells from triggering the Th1 program, was attenuated too in the presence of calcitriol. Ectopic expression of either Gfi1 or VDR impaired the secretion of IL-13 but not IL-4 in Th2 cells. Ecr, a common conserved region, enhanced the transactivation of bothIl4, andIl13promoter, which got attenuated in the presence of calcitriol. Calcitriol interfered withIl13promoter activation but notIl4promoter activation, which was Gata3-dependent but Ecr-independent. As a repressor Gfi1 significantly impairedIl13promoter activation; addition of calcitriol failed to alter the promoter activity. In murine Th2 cells, VDR interacted with Gata3 but not Gfi1. Calcitriol augmented the recruitment of VDR toIl13promoter and Ecr regions, exceptIl4promoter. Gata3 recruitment was significantly impaired atIl13and Ecr locus in the presence of calcitriol but increased atIl4promoter. However, in the presence of calcitriol the overall recruitment of Gfi1 remained unchanged atIl4but increased atIl13locus in Th2 cells. Calcitriol elicited distinct histone modifications atIl4andIl13gene loci. Together, our studies elucidated the molecular mechanisms behind calcitriol-mediated regulation of Th2 cell differentiation.Abstract Figure

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Section: Resultsmentioning

confidence: 99%

Section: Name Of the Primersmentioning

confidence: 99%

Calcitriol impairs the secretion of IL-4 and IL-13 in Th2 cells via modulating VDR-Gata3-Gfi1 axis

Biswas,

Chattopadhyay,

Hazra

et al. 2023

Preprint

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“…Of this protein bunch, of significant interest is histone deacetylase (HDAC 1), which was present in the samples from D16 until parturition (M5). This protein might contribute to stress alleviation since it is involved in cell differentiation both in the embryo and maternal organism and in signal transduction specifically related to immune response and histone H3 and H4 deacetylation [47,48]. Studies have proven that a reduction in HDAC 1 concentration is directly linked to abnormalities caused by stress in early life [48].…”

Section: Discussionmentioning

confidence: 99%

Proteomics Analysis of Pregnancy in Ewes under Heat Stress Conditions and Melatonin Administration

Bouroutzika,

Proikakis,

Theodosiadou

et al. 2024

Animals

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Melatonin is an indoleamine with broad spectrum properties that acts as a regulator of antioxidant and immune response in organisms. In our previous studies, melatonin improved redox status and inflammatory response in pregnant ewes under heat stress conditions. In the present study, using proteomics, the proteins regulated by melatonin during different stages of pregnancy and lambing were assessed. Twenty-two ewes equally divided into two groups, the melatonin (M) (n = 11) and control (C) group (n = 11), participated in the study and were exposed to heat stress during the first months of pregnancy. In the M group, melatonin implants were administered throughout pregnancy, every 40 days, until parturition (a total of four implants per ewe). Blood samples were collected at the beginning of the study simultaneously with the administration of the first melatonin implant (blood samples M1, C1), mating (M2, C2), second implant (M3, C3), fourth implant (M4, C4) and parturition (M5, C5), and MALDI-TOF analysis was performed. The results revealed the existence of 42 extra proteins in samples M2, M3 and M4 and 53 in M5 (sample at parturition) that are linked to melatonin. The biological processes of these proteins refer to boosted immune response, the alleviation of oxidative and endoplasmic reticulum stress, energy metabolism, the protection of the maternal organism and embryo development. This proteomics analysis indicates that melatonin regulates protective mechanisms and controls cell proliferation under exogenous or endogenous stressful stimuli during pregnancy and parturition.

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“…MDM2 E3 ligase mediates ubiquitination and degradation of HDAC1 in vascular calcification 45 . Although HDAC1 plays a vital role in Th cell function and differentiation 14 , its regulation through ubiquitination in CD4 + T cells remains to be clarified. In this study, we found that RNF157 is a key ubiquitination regulator of HDAC1.…”

Section: Discussionmentioning

confidence: 99%

RNF157 attenuates CD4⁺ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation

Wang¹,

Zhao²,

Tan³

et al. 2023

Theranostics

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Background: CD4 + T cells play an important role in body development and homeostasis. Quantitative and functional changes in CD4 + T cells result in abnormal immune responses, which lead to inflammation, cancer, or autoimmune diseases, such as multiple sclerosis (MS). Ubiquitination plays an essential role in the differentiation and functioning of CD4 + T cells. However, the function of several E3 ubiquitin ligases in CD4 + T cell differentiation and T cell-mediated pathological diseases remains unclear. Methods: RNA sequencing data were analyzed to identify the E3 ubiquitin ligases that participate in the pathogenesis of MS. Furthermore, conditional knockout mice were generated. Specifically, flow cytometry, qPCR, western blot, CO-IP and cell transfer adoptive experiments were performed. Results: In this study, we identified The RING finger 157 (RNF157) as a vital regulator of CD4 + T cell differentiation; it promoted Th1 differentiation but attenuated Th17 differentiation and CCR4 and CXCR3 expressions in CD4 + T cells, thereby limiting experimental autoimmune encephalomyelitis development. Mechanistically, RNF157 in CD4 + T cells targeted HDAC1 for K48-linked ubiquitination and degradation. Notably, RNF157 expression was significantly decreased and showed a significant negative correlation with RORγt expression in patients with MS. Conclusions: Our study highlights the critical role of RNF157 in regulating CD4 + T cell functions in autoimmune diseases and suggests RNF157 as a potential target in adaptive immune responses against MS and other autoimmune disorders.

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The emerging role of histone deacetylase 1 in allergic diseases

Cited by 7 publications

References 93 publications

Calcitriol impairs the secretion of IL-4 and IL-13 in Th2 cells via modulating VDR-Gata3-Gfi1 axis

Calcitriol impairs the secretion of IL-4 and IL-13 in Th2 cells via modulating VDR-Gata3-Gfi1 axis

Proteomics Analysis of Pregnancy in Ewes under Heat Stress Conditions and Melatonin Administration

RNF157 attenuates CD4⁺ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation

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The emerging role of histone deacetylase 1 in allergic diseases

Cited by 7 publications

References 93 publications

Calcitriol impairs the secretion of IL-4 and IL-13 in Th2 cells via modulating VDR-Gata3-Gfi1 axis

Calcitriol impairs the secretion of IL-4 and IL-13 in Th2 cells via modulating VDR-Gata3-Gfi1 axis

Proteomics Analysis of Pregnancy in Ewes under Heat Stress Conditions and Melatonin Administration

RNF157 attenuates CD4+ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation

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RNF157 attenuates CD4⁺ T cell-mediated autoimmune response by promoting HDAC1 ubiquitination and degradation