reveal the molecular mechanism of varieties of inflammatory diseases, but also develop novel theranostical strategies against these diseases. This Research Topic is the Volume II continually collecting the excellent works about "Epigenetics of the Immune Component of Inflammation" and a total of 9 articles from 77 authors were accepted, which demonstrates great interests of this topic in this field and deepens a better understanding of epigenetic regulation in immune diseases and inflammation responses, and highlights the clinical significance of epigenetic regulation and inflammatory immune components in disease theranostics. This topic can be roughly divided into the 3 following subtopics:
The genome modifications mediate the progression of inflammatory diseases via modulating expression of related inflammatory genes [28]. In our special issue, Katarzyna et al. found that DNA methyltransferase (DNMT) inhibitors decitabine could suppress proliferation of gingival fibroblasts (GFs) and induce necrotic cell death via reducing genome methylation. RNA sequencing showed that decitabine raised chemokines CCL-5, -8, -13, and -20, and IL-1A, -18, -33, CSF3, and matrix metalloproteinases MMP-1, -9, and -13, and intercellular adhesion molecule-1 (ICAM-1), and reduced genes mediated collagen fibril and extracellular matrix organization, which suggest that DNMT inhibitors are potential agents against periodontitis pathogenesis. However, the potential cytotoxicity of DNMT inhibitor is nonnegligible challenge for their clinical applications. Jiang et al. explored the methylation level of Homeodomain-interacting protein kinase 3 (HIPK3) in blood using a sample database including 235 RA patients, 30 osteoarthritis (OA) patients, and 30 matched healthy controls. The results revealed that all 7 CpG islands are hypomethylated in RA patients compared with OA and healthy individuals. The 33286785 CpG displays the highest predictive power (AUC=0.829) against RA and the prediction model could be further improved by combining HIPK3 with clinical indexes rheumatoid factor (RF + ) and anti-citrullinated protein antibodies (ACPA -). Moreover, their study also found that the methylated HIPK3 levels is negatively correlated with Creactive protein (CRP), suggesting that blood methylation level of HIPK3 has the potential as a clinical diagnostic biomarker and indicator for CRP in RA. Shan et al. summarized the latest application advancement of the gamma-aminobutyric acid (GABA)ergic system (mainly consists of GABA, GABA transporter, and GABA-related receptors) in RA theranostics, which provides an insight into the potential theoretical guidance and clinical choices for RA therapy. Zheng et al. summed up the functions of serine proteases granzymes (Gzms) in RA pathogenesis and considered that these enzymes are potential targets for diagnosis and therapy for RA. Valentina et al.'s study found that the DNA methylation profiles in CD4 + T-cells could discriminate disease status of healthy controls, skin psoriasis and psoriatic arthritis, which suggests that DNA methylation imprints may be used to determine the degree and grade of psoriasis, and thus help carry out individualized therapeutic strategy accordingly. Sapienza et al revealed that distinction in DNA methylation profile of diabetes patients with eventually develop end-stage renal disease (ESRD) and without diabetic nephropathy (DN) [29], and Wang et al. considered that this profile could use to discriminate diabetes with ESRD and without DN. Zhang et al. described the immunoregulatoryand metabolic roles and action mechanisms of genome methylation modification in the progression of metabolicassociated fatty liver disease (MAFLD), which provides references for the diagnosis and treatment of MAFLD via targeting nucleotide methylation. Xue et al. found that 8-oxoguanine DNA glycosylase1 (OGG1) inhibition or ablation enhances the antiviral activity of epithelial cells to infection of human respiratory syncytial virus (RSV) in vitro and in vivo. Further study revealed that OGG1 recognize the 8-oxoGua in vicinity of interferon response elements (IRF) within IFN-λ promoter, and thus reduces DNA occupancy of NF-κB/RelA and IRFs via promoting the interaction between NF-κB homodimer p50 and p50 in guanine islets (5'-GGG-3') in IFN-λ promoter, which reduces IFN-λ production, increases viral load and neutrophilia, and finally aggravates viral infection and immunopathology in mice. This finding indicates that OGG1 is a potential target for eliminating pulmonary viral infections in clinical.
Post-transcriptional modification refers to the various changes and alterations of RNA molecules after transcription from DNA [30]. Post-transcriptional modifications including microRNA, lncRNA, tRNA, m 6 A modifications, etc. mediate various inflammatory diseases via modulating multiple immune components. Wang et al. systematically summarized the dysregulation of miRNAs miR-183/96/182 cluster (miR-183C) in many autoimmune disorders, such as systemic multiple sclerosis, ocular autoimmune diseases, and lupus erythematosus, and highlighted the potential of miR-183C as targets for diagnosis markers and therapy against these autoimmune diseases. Wang et al. described the functions and mechanisms of non-coding RNAs including microRNAs, lncRNAs and m 6 A modifications in symptoms of podocytopathies, which provides a theoretical basis and target selection for the diagnosis and treatment of DN.
Post-translational modifications are also crucial epigenetic modes involved in accurately orchestrating varieties of inflammatory process via writing, reading, and erasing marks of specific amino acid residues within proteins [31]. Wang et al. considered that histone acetylation/de acetylation modification in podocytopathy contribute to protecting from DN progression, which are potential targets for DN therapy.
