NFIL3 deficiency alleviates EAE through regulating different immune cell subsets

Chen, Zhigang; Fan, Rong; Liang, Jie; Xiao, Zexiu; Dang, Junlong; Zhao, Jun; Weng, Ruihui; Zhu, Cansheng; Zheng, Song Guo; Jiang, Ying

doi:10.1016/j.jare.2021.10.011

Cited by 10 publications

(6 citation statements)

References 47 publications

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“…The detection of REST and SUZ12 is consistent with studies demonstrating the role of these factors as a master repressor of neuronal gene expression in mouse hippocampus during the neurodevelopment phase [53,54]. Likewise, nuclear factor interleukin-3 (NFIL3) has been associated with innate and adaptive immunity processes (i.e., natural killer cells, B cells, and macrophages) and immune-mediated diseases [55]. SMARCA4 has been associated with MIA-related autism spectrum disorder [56], and the nuclear factor kappa B subunit 1 (NFKB1) enrichment is aligned with the low-level chronic inflammation and enhanced response to an inflammatory stimulus in a knockout mouse model [57].…”

Section: Regulatory Motifs and Transcription Factors Impacted By Mate...supporting

confidence: 84%

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Rodríguez-Zas

Southey

Rymut

et al. 2022

Genes

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The hippocampus participates in spatial navigation and behavioral processes, displays molecular plasticity in response to environmental challenges, and can play a role in neuropsychiatric diseases. The combined effects of inflammatory prenatal and postnatal challenges can disrupt the hippocampal gene networks and regulatory mechanisms. Using a proven pig model of viral maternal immune activation (MIA) matched to controls and an RNA-sequencing approach, the hippocampal transcriptome was profiled on two-month-old female and male offspring assigned to fasting, mimetic viral, or saline treatments. More than 2600 genes presented single or combined effects (FDR-adjusted p-value < 0.05) of MIA, postnatal stress, or sex. Biological processes and pathways encompassing messenger cyclic adenosine 3′,5′-monophosphate (cAMP) signaling were enriched with genes including gastric inhibitory polypeptide receptor (GIPR) predominantly over-expressed in the MIA-exposed fasting males relative to groups that differed in sex, prenatal or postnatal challenge. While this pattern was amplified in fasting offspring, the postnatal inflammatory challenge appeared to cancel out the effects of the prenatal challenge. The transcription factors C-terminal binding protein 2 (CTBP2), RE1 silencing transcription factor (REST), signal transducer and activator of transcription 1 (STAT1), and SUZ12 polycomb repressive complex 2 subunit were over-represented among the genes impacted by the prenatal and postnatal factors studied. Our results indicate that one environmental challenge can influence the effect of another challenge on the hippocampal transcriptome. These findings can assist in the identification of molecular targets to ameliorate the effects of pre-and post-natal stressors on hippocampal-associated physiology and behavior.

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Section: Regulatory Motifs and Transcription Factors Impacted By Mate...supporting

confidence: 84%

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Rodríguez-Zas

Southey

Rymut

et al. 2022

Genes

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“…In addition, CD11C + cells are crucial myeloid cells that preserve antigen presenting function, serving as principal drivers of autoimmune‐related pathology and have been used in studies of the mutual effect between Th17 cells and antigen presenting cells. 38 , 53 , 54 Additionally, the level of infiltrated CD11C + myeloid cells under the anti‐GM‐CSF treatment displayed trends consistent with those of CD4 + TCs (Figure 5D ). These findings indicate that anti‐GM‐CSF treatment decreased intraocular inflammation, which is consistent with the clinical and histopathological results.…”

Section: Resultsmentioning

confidence: 54%

“…After anti‐GM‐CSF treatment, this infiltration was significantly reduced (Figure 5C, Supporting Information Figure S6A). In addition, CD11C + cells are crucial myeloid cells that preserve antigen presenting function, serving as principal drivers of autoimmune‐related pathology and have been used in studies of the mutual effect between Th17 cells and antigen presenting cells 38,53,54 . Additionally, the level of infiltrated CD11C + myeloid cells under the anti‐GM‐CSF treatment displayed trends consistent with those of CD4 + TCs (Figure 5D).…”

Section: Resultsmentioning

confidence: 87%

Sleep loss potentiates Th17‐cell pathogenicity and promotes autoimmune uveitis

Liu

Huang

et al. 2023

Clinical & Translational Med

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Background Sleep loss (SL) is a health issue associated with the higher risk of autoimmune and inflammatory disorders. However, the connection between SL, the immune system, and autoimmune diseases remains unknown. Methods We conducted mass cytometry, single‐cell RNA sequencing, and flow cytometry to analyze how SL influences immune system and autoimmune disease development. Peripheral blood mononuclear cells from six healthy subjects before and after SL were collected and analyzed by mass cytometry experiments and subsequent bioinformatic analysis to identify the effects of SL on human immune system. Sleep deprivation and experimental autoimmune uveitis (EAU) mice model were constructed, and scRNA‐seq data from mice cervical draining lymph nodes were generated to explore how SL influences EAU development and related autoimmune responses. Results We found compositional and functional changes in human and mouse immune cells after SL, especially in effector CD4 + T and myeloid cells. SL upregulated serum GM‐CSF levels in healthy individuals and in patients with SL‐induced recurrent uveitis. Experiments in mice undergoing SL or EAU demonstrated that SL could aggravate autoimmune disorders by inducing pathological immune cell activation, upregulating inflammatory pathways, and promoting intercellular communication. Furthermore, we found that SL promoted Th17 differentiation, pathogenicity, and myeloid cells activation through the IL‐23Th17GM‐CSF feedback mechanism, thus promoting EAU development. Lastly, an anti‐GM‐CSF treatment rescued SL‐induced EAU aggravation and pathological immune response. Conclusions SL promoted Th17 cells pathogenicity and autoimmune uveitis development, especially through the interaction between Th17 and myeloid cells involving GM‐CSF signaling, providing possible therapeutic targets for the SL‐related pathological disorders.

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“… 45 For example, NFIL3 has been found to be related to immune-mediated diseases, like SLE, arthritis and Crohn’s disease. 46 In addition, some studies have demonstrated that NFIL3 may regulate the pathological process of heart failure through calcium signaling mechanisms, autocrine signaling, and insulin-like growth factor II receptor. 47 Our experiments confirm that NFIL3 is highly expressed in ischemic myocardial tissue and may be involved in neutrophil-mediated cell damage.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Hub Genes Related to Neutrophil Extracellular Traps-Mediated Cell Damage During Myocardial Infarction

Ke,

Ni,

Yuan

et al. 2024

JIR

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Purpose Studies have shown that neutrophil-mediated formation of neutrophil extracellular traps (NETs) leads to increased inflammatory response and cellular tissue damage during myocardial infarction (MI). We aimed to identify and validate possible hub genes in the process of NETs-mediated cell damage. Methods We performed an immune cell infiltration analysis of the MI transcriptome dataset based on CIBERSORT and ssGSEA algorithms. Gene expression profiles of NETs formation (GSE178883) were used to analyze the physiological processes of peripheral blood neutrophils after phorbol myristate acetate (PMA) stimulation. Bioinformatics and machine learning algorithms were utilized to find candidate hub genes based on NETs-related genes and transcriptome datasets (GSE66360 and GSE179828). We generated the receiver operating curve (ROC) to evaluate the diagnostic value of hub genes. Next, the correlation between hub genes and immune cells was analyzed using CIBERSORT, ssGSEA and xCell algorithms. Finally, we used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to verify gene expression. Results Immune cell infiltration analysis revealed that inflammatory cells such as neutrophils were highly expressed in the peripheral blood of patients with MI. Functional analysis of differentially expressed genes (DEGs) in GSE178883 indicated that the potential pathogenesis lies in immune terms. Using weighted gene co-expression network analysis (WGCNA) and machine learning algorithms, we finally identified the seven hub genes (FCAR, IL1B, MMP9, NFIL3, CXCL2, ICAM1, and ZFP36). The qRT-PCR results showed that IL-1B, MMP9, and NFIL3 mRNA expression was up-regulated in the MI group compared to the control. Immunohistochemical results showed high MMP9, IL-1B, and NFIL3 expression in the infarcted area compared to the non-infarcted area and sham-operated groups. Conclusion We identified seven hub genes associated with NETs-mediated cellular damage during MI. Our results may provide insights into the mechanisms of neutrophil-mediated cell injury during MI.

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NFIL3 deficiency alleviates EAE through regulating different immune cell subsets

Cited by 10 publications

References 47 publications

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Sleep loss potentiates Th17‐cell pathogenicity and promotes autoimmune uveitis

Identification and Validation of Hub Genes Related to Neutrophil Extracellular Traps-Mediated Cell Damage During Myocardial Infarction

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