1 6255 107 THE MICROBIOTA AND EPIGENETIC REGULATION OF T HELPER 17/REGULATORY T CELLS: IN SEARCH OF A BALANCED IMMUNE SYSTEM. IMMUNE CELLS NOT ONLY AFFECT TISSUE HOMEOSTASIS AT THE SITE OF INFLAMMATION BUT ALSO EXERT SYSTEMIC EFFECTS CONTRIBUTING TO MULTIPLE CHRONIC CONDITIONS. RECENT EVIDENCE CLEARLY SUPPORTS AN ALTERED T HELPER 17/REGULATORY T CELL (TH17/TREG) BALANCE LEADING TO THE DEVELOPMENT AND PROGRESSION OF INFLAMMATORY DISEASES THAT NOT ONLY AFFECT THE GASTROINTESTINAL TRACT BUT ALSO HAVE WHOLE-BODY MANIFESTATIONS, INCLUDING INSULIN RESISTANCE. EPIGENETIC MECHANISMS ARE AMENABLE TO BOTH ENVIRONMENTAL AND CIRCULATING FACTORS AND CONTRIBUTE TO DETERMINING THE T CELL LANDSCAPE. THE RECENTLY IDENTIFIED PARTICIPATION OF THE GUT MICROBIOTA IN THE REMODELING OF THE EPIGENOME OF IMMUNE CELLS HAS TRIGGERED A PARADIGM SHIFT IN OUR UNDERSTANDING OF THE ETIOLOGY OF VARIOUS INFLAMMATORY DISEASES AND OPENED NEW PATHS TOWARD THERAPEUTIC STRATEGIES. IN THIS REVIEW, WE PROVIDE AN OVERVIEW OF THE CONTRIBUTION OF THE TH17/TREG BALANCE IN THE DEVELOPMENT AND PROGRESSION OF INFLAMMATORY BOWEL DISEASES AND METABOLIC DISEASES. WE DISCUSS THE INVOLVEMENT OF EPIGENETIC MECHANISMS IN THE REGULATION OF T CELL FUNCTION IN THE PARTICULAR CONTEXT OF DYSBIOSIS. FINALLY, WE EXAMINE THE POTENTIAL FOR NUTRITIONAL INTERVENTIONS AFFECTING THE GUT MICROBIOTA TO RESHAPE THE T CELL EPIGENOME AND ADDRESS THE INFLAMMATORY COMPONENT OF VARIOUS DISEASES. 2017 2 5932 32 TARGETING EPIGENETIC REGULATORS FOR INFLAMMATION: MECHANISMS AND INTERVENTION THERAPY. EMERGING EVIDENCE INDICATES THAT RESOLUTION OF INFLAMMATION IS A CRITICAL AND DYNAMIC ENDOGENOUS PROCESS FOR HOST TISSUES DEFENDING AGAINST EXTERNAL INVASIVE PATHOGENS OR INTERNAL TISSUE INJURY. IT HAS LONG BEEN KNOWN THAT AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATORY DISORDERS ARE CHARACTERIZED BY DYSREGULATED IMMUNE RESPONSES, LEADING TO EXCESSIVE AND UNCONTROL TISSUE INFLAMMATION. THE DYSREGULATION OF EPIGENETIC ALTERATIONS INCLUDING DNA METHYLATION, POSTTRANSLATIONAL MODIFICATIONS TO HISTONE PROTEINS, AND NONCODING RNA EXPRESSION HAS BEEN IMPLICATED IN A HOST OF INFLAMMATORY DISORDERS AND THE IMMUNE SYSTEM. THE INFLAMMATORY RESPONSE IS CONSIDERED AS A CRITICAL TRIGGER OF EPIGENETIC ALTERATIONS THAT IN TURN INTERCEDE INFLAMMATORY ACTIONS. THUS, UNDERSTANDING THE MOLECULAR MECHANISM THAT DICTATES THE OUTCOME OF TARGETING EPIGENETIC REGULATORS FOR INFLAMMATORY DISEASE IS REQUIRED FOR INFLAMMATION RESOLUTION. IN THIS ARTICLE, WE ELUCIDATE THE CRITICAL ROLE OF THE NUCLEAR FACTOR-KAPPAB SIGNALING PATHWAY, JAK/STAT SIGNALING PATHWAY, AND THE NLRP3 INFLAMMASOME IN CHRONIC INFLAMMATORY DISEASES. AND WE FORMULATE THE RELATIONSHIP BETWEEN INFLAMMATION, CORONAVIRUS DISEASE 2019, AND HUMAN CANCERS. ADDITIONALLY, WE REVIEW THE MECHANISM OF EPIGENETIC MODIFICATIONS INVOLVED IN INFLAMMATION AND INNATE IMMUNE CELLS. ALL THAT MATTERS IS THAT WE PROPOSE AND DISCUSS THE REJUVENATION POTENTIAL OF INTERVENTIONS THAT TARGET EPIGENETIC REGULATORS AND REGULATORY MECHANISMS FOR CHRONIC INFLAMMATION-ASSOCIATED DISEASES TO IMPROVE THERAPEUTIC OUTCOMES. 2022 3 1876 31 EMERGING ROLES FOR EPIGENETIC PROGRAMMING IN THE CONTROL OF INFLAMMATORY SIGNALING INTEGRATION IN HEATH AND DISEASE. MACROPHAGES AND DENDRITIC CELLS INITIATE THE INNATE IMMUNE RESPONSE TO INFECTION AND INJURY AND CONTRIBUTE TO INFLAMMATORY SIGNALING TO MAINTAIN THE HOMEOSTASIS OF VARIOUS TISSUES, WHICH INCLUDES RESIDENT MACROPHAGES FOR THE ELIMINATION OF INVADING MICROORGANISMS AND TISSUE DAMAGE. INAPPROPRIATE INFLAMMATORY SIGNALING CAN LEAD TO PERSISTENT INFLAMMATION AND FURTHER DEVELOP INTO AUTOIMMUNE AND INFLAMMATION-ASSOCIATED DISEASES. INFLAMMATORY SIGNALING PATHWAYS HAVE BEEN WELL CHARACTERIZED, BUT HOW THESE SIGNALING PATHWAYS ARE CONVERTED INTO SUSTAINED AND DIVERSE PATTERNS OF EXPRESSION OF CYTOKINES, CHEMOKINES, AND OTHER GENES IN RESPONSE TO ENVIRONMENTAL CHALLENGES IS UNCLEAR. EMERGING EVIDENCE SUGGESTS THE IMPORTANT ROLE OF EPIGENETIC MECHANISMS IN FINELY TUNING THE OUTCOME OF THE HOST INNATE IMMUNE RESPONSE. AN UNDERSTANDING OF EPIGENETIC REGULATION OF INNATE IMMUNE CELL IDENTITY AND FUNCTION WILL ENABLE THE IDENTIFICATION OF THE MECHANISM BETWEEN GENE-SPECIFIC HOST DEFENSES AND INFLAMMATORY DISEASE AND WILL ALSO ALLOW FOR EXPLORATION OF THE PROGRAM OF INNATE IMMUNE MEMORY IN HEALTH AND DISEASE. THIS INFORMATION COULD BE USED TO DEVELOP THERAPEUTIC AGENTS TO ENHANCE THE HOST RESPONSE, PREVENTING CHRONIC INFLAMMATION THROUGH PRESERVING TISSUES AND SIGNALING INTEGRITY. 2017 4 6200 38 THE INFLAMMATORY EFFECT OF EPIGENETIC FACTORS AND MODIFICATIONS IN TYPE 2 DIABETES. INFLAMMATION HAS A CENTRAL ROLE IN THE ETIOLOGY OF TYPE 2 DIABETES (T2D) AND ITS COMPLICATIONS. BOTH GENETIC AND EPIGENETIC FACTORS HAVE BEEN IMPLICATED IN THE DEVELOPMENT OF T2D-ASSOCIATED INFLAMMATION. EPIGENETIC MECHANISMS REGULATE THE FUNCTION OF SEVERAL COMPONENTS OF THE IMMUNE SYSTEM. DIABETIC CONDITIONS TRIGGER ABERRANT EPIGENETIC ALTERATIONS THAT CONTRIBUTE TO THE PROGRESSION OF INSULIN RESISTANCE AND BETA-CELL DYSFUNCTION BY INDUCTION OF INFLAMMATORY RESPONSES. THUS, TARGETING EPIGENETIC FACTORS AND MODIFICATIONS, AS ONE OF THE UNDERLYING CAUSES OF INFLAMMATION, COULD LEAD TO THE DEVELOPMENT OF NOVEL IMMUNE-BASED STRATEGIES FOR THE TREATMENT OF T2D. THE AIM OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE EPIGENETIC MECHANISMS INVOLVED IN THE PROPAGATION AND PERPETUATION OF CHRONIC INFLAMMATION IN T2D. WE ALSO DISCUSS THE POSSIBLE ANTI-INFLAMMATORY APPROACHES THAT TARGET EPIGENETIC FACTORS FOR THE TREATMENT OF T2D. 2020 5 2070 26 EPIGENETIC CONTROL OF SKIN IMMUNITY. EPIGENETICS HAS BEEN WELL UNDERSTOOD FOR ITS ROLE IN CELL DEVELOPMENT; HOWEVER, IT IS NOW KNOWN TO REGULATE MANY PROCESSES INVOLVED IN IMMUNE CELL ACTIVATION IN A VARIETY OF CELLS. THE SKIN MAINTAINS HOMEOSTASIS VIA CROSSTALK BETWEEN IMMUNE AND NON-IMMUNE CELLS. DISRUPTION OF NORMAL EPIGENETIC REGULATION IN THESE CELLS MAY ALTER THE TRANSCRIPTION OF IMMUNE-REGULATORY FACTORS AND AFFECT THE IMMUNOLOGICAL BALANCE IN THE SKIN. THIS REVIEW SUMMARIZES RECENT EVIDENCE FOR THE EPIGENETIC REGULATION OF SKIN IMMUNITY. MUCH OF WHAT IS KNOWN ABOUT EPIGENETIC INVOLVEMENT IN SKIN IMMUNITY IS ASSOCIATED WITH DNA METHYLATION. THIS REVIEW FOCUSES ON EPIGENETIC REGULATION OF HISTONE MODIFICATION AND CHROMATIN REMODELING AND DESCRIBES THEIR ROLE IN THE TRANSCRIPTIONAL REGULATION OF IMMUNE-REGULATORY FACTORS. WHILE MUCH IS STILL UNKNOWN REGARDING THE REGULATION OF SKIN IMMUNITY VIA HISTONE MODIFICATION OR CHROMATIN REMODELING, THESE PROCESSES MAY UNDERLIE THE PATHOGENESIS OF CHRONIC CUTANEOUS IMMUNE DISORDERS. 2023 6 6344 29 THE ROLE OF EPIGENETICS IN AGING AND AUTOIMMUNITY. THE DECLINE IN IMMUNOCOMPETENCE WITH AGE IS ACCOMPANIED BY THE INCREASE IN THE INCIDENCE OF AUTOIMMUNE DISEASES. AGING OF THE IMMUNE SYSTEM, OR IMMUNOSENESCENCE, IS CHARACTERIZED BY A DECLINE OF BOTH T AND B CELL FUNCTION, AND PARADOXICALLY THE PRESENCE OF LOW-GRADE CHRONIC INFLAMMATION. THERE IS GROWING EVIDENCE THAT EPIGENETICS, THE STUDY OF INHERITED CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED BY THE DNA SEQUENCE ITSELF, CHANGES WITH AGING. INTERESTINGLY, EMERGING EVIDENCE SUGGESTS A KEY ROLE FOR EPIGENETICS IN HUMAN PATHOLOGIES, INCLUDING INFLAMMATORY AND NEOPLASTIC DISORDERS. HERE, WE WILL REVIEW THE POTENTIAL MECHANISMS THAT CONTRIBUTE TO THE INCREASE IN AUTOIMMUNE RESPONSES IN AGING. IN PARTICULAR, WE WILL DISCUSS HOW EPIGENETIC ALTERATIONS, ESPECIALLY DNA METHYLATION AND HISTONE ACETYLATION, ARE ACCUMULATED DURING AGING AND HOW THESE EVENTS CONTRIBUTE TO AUTOIMMUNITY RISK. 2010 7 6496 41 TRAINED IMMUNITY CONTRIBUTION TO AUTOIMMUNE AND INFLAMMATORY DISORDERS. A DYSREGULATED IMMUNE RESPONSE TOWARD SELF-ANTIGENS CHARACTERIZES AUTOIMMUNE AND AUTOINFLAMMATORY (AIF) DISORDERS. AUTOANTIBODIES OR AUTOREACTIVE T CELLS CONTRIBUTE TO AUTOIMMUNE DISEASES, WHILE AUTOINFLAMMATION RESULTS FROM A HYPER-FUNCTIONAL INNATE IMMUNE SYSTEM. ASIDE FROM THEIR DIFFERENCES, MANY STUDIES SUGGEST THAT MONOCYTES AND MACROPHAGES (MO/MA) SIGNIFICANTLY CONTRIBUTE TO THE DEVELOPMENT OF BOTH TYPES OF DISEASE. MO/MA ARE INNATE IMMUNE CELLS THAT PROMOTE AN IMMUNE-MODULATORY, PRO-INFLAMMATORY, OR REPAIR RESPONSE DEPENDING ON THE MICROENVIRONMENT. HOWEVER, UNDERSTANDING THE CONTRIBUTION OF THESE CELLS TO DIFFERENT IMMUNE DISORDERS HAS BEEN DIFFICULT DUE TO THEIR HIGH FUNCTIONAL AND PHENOTYPIC PLASTICITY. SEVERAL FACTORS CAN INFLUENCE THE FUNCTION OF MO/MA UNDER THE LANDSCAPE OF AUTOIMMUNE/AUTOINFLAMMATORY DISEASES, SUCH AS GENETIC PREDISPOSITION, EPIGENETIC CHANGES, OR INFECTIONS. FOR INSTANCE, SOME VACCINES AND MICROORGANISMS CAN INDUCE EPIGENETIC CHANGES IN MO/MA, MODIFYING THEIR FUNCTIONAL RESPONSES. THIS PHENOMENON IS KNOWN AS TRAINED IMMUNITY. TRAINED IMMUNITY CAN BE MEDIATED BY MO/MA AND NK CELLS INDEPENDENTLY OF T AND B CELL FUNCTION. IT IS DEFINED AS THE ALTERED INNATE IMMUNE RESPONSE TO THE SAME OR DIFFERENT MICROORGANISMS DURING A SECOND ENCOUNTER. THE IMPROVEMENT IN CELL FUNCTION IS RELATED TO EPIGENETIC AND METABOLIC CHANGES THAT MODIFY GENE EXPRESSION. ALTHOUGH THE BENEFITS OF IMMUNE TRAINING HAVE BEEN HIGHLIGHTED IN A VACCINATION CONTEXT, THE EFFECTS OF THIS TYPE OF IMMUNE RESPONSE ON AUTOIMMUNITY AND CHRONIC INFLAMMATION STILL REMAIN CONTROVERSIAL. INDUCTION OF TRAINED IMMUNITY REPROGRAMS CELLULAR METABOLISM IN HEMATOPOIETIC STEM CELLS (HSCS), TRANSMITTING A MEMORY-LIKE PHENOTYPE TO THE CELLS. THUS, TRAINED MO/MA DERIVED FROM HSCS TYPICALLY PRESENT A METABOLIC SHIFT TOWARD GLYCOLYSIS, WHICH LEADS TO THE MODIFICATION OF THE CHROMATIN ARCHITECTURE. DURING TRAINED IMMUNITY, THE EPIGENETIC CHANGES FACILITATE THE SPECIFIC GENE EXPRESSION AFTER SECONDARY CHALLENGE WITH OTHER STIMULI. CONSEQUENTLY, THE ENHANCED PRO-INFLAMMATORY RESPONSE COULD CONTRIBUTE TO DEVELOPING OR MAINTAINING AUTOIMMUNE/AUTOINFLAMMATORY DISEASES. HOWEVER, THE PREDICTION OF THE OUTCOME IS NOT SIMPLE, AND OTHER STUDIES PROPOSE THAT TRAINED IMMUNITY CAN INDUCE A BENEFICIAL RESPONSE BOTH IN AIF AND AUTOIMMUNE CONDITIONS BY INDUCING ANTI-INFLAMMATORY RESPONSES. THIS ARTICLE DESCRIBES THE METABOLIC AND EPIGENETIC MECHANISMS INVOLVED IN TRAINED IMMUNITY THAT AFFECT MO/MA, CONTRAPOSING THE CONTROVERSIAL EVIDENCE ON HOW IT MAY IMPACT AUTOIMMUNE/AUTOINFLAMMATION CONDITIONS. 2022 8 4392 28 MODIFIABLE RISK FACTORS IN PERIODONTAL DISEASE: EPIGENETIC REGULATION OF GENE EXPRESSION IN THE INFLAMMATORY RESPONSE. EPIGENETICS AS A MODIFIABLE RISK FACTOR IN PERIODONTAL DISEASES HAS BEEN INVESTIGATED IN LIGHT OF THE CURRENT KNOWLEDGE OF HOW CHRONIC INFECTION AND INFLAMMATION CAN AFFECT GENE-SPECIFIC EPIGENETIC REPROGRAMMING IN PERIODONTAL TISSUES. EPIGENOMIC PROGRAMMING MIGHT BE PARTICULARLY SENSITIVE TO ENVIRONMENTAL INFLUENCES, AND A COMBINATION OF PHYSIOLOGICAL STRESSORS AND ENVIRONMENTAL EXPOSURES APPEARS TO AFFECT THE EPIGENOMIC PROGRAM ACQUIRED BY A CELL DURING DIFFERENTIATION AND THROUGHOUT THE CELLULAR LINEAGE LIFESPAN. VIRAL AND BACTERIAL INFECTIONS CAN ESTABLISH SEVERAL TYPES OF EPIGENETIC MODIFICATIONS, WHICH SOMETIMES ENGAGE IN A COMPLEX EPIGENETIC CROSSTALK ALSO REFLECTING IN THE ESTABLISHMENT AND PROGRESS OF PERIODONTAL DISEASES. THE INFLAMMATORY AND METABOLIC STATES OF THE PERIODONTAL TISSUES ARE DRIVEN BY THE INFECTIOUS STIMULI, AND THE MAGNITUDE OF THE CELLULAR AND MOLECULAR SIGNATURE RESPONSE IS FURTHER DICTATED BY THE HOST GENETIC AND EPIGENETIC TRAITS ASSOCIATED WITH VARIOUS SYSTEMIC EXPOSURES, INCLUDING SMOKING, OBESITY AND DIABETES/HYPERGLYCEMIA. THIS REVIEW DISCUSSES THE ADVANCES IN EPIGENETICS, FOCUSING ON THE ROLE OF DNA METHYLATION IN THE PATHOGENESIS OF PERIODONTAL DISEASE AND THE POTENTIAL OF EPIGENETIC THERAPY. 2014 9 6006 34 THE ALTERATIONS IN AND THE ROLE OF THE TH17/TREG BALANCE IN METABOLIC DISEASES. CHRONIC INFLAMMATION PLAYS AN IMPORTANT ROLE IN THE DEVELOPMENT OF METABOLIC DISEASES. THESE INCLUDE OBESITY, TYPE 2 DIABETES MELLITUS, AND METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE. THE PROINFLAMMATORY ENVIRONMENT MAINTAINED BY THE INNATE IMMUNITY, INCLUDING MACROPHAGES AND RELATED CYTOKINES, CAN BE INFLUENCED BY ADAPTIVE IMMUNITY. THE FUNCTION OF T HELPER 17 (TH17) AND REGULATORY T (TREG) CELLS IN THIS PROCESS HAS ATTRACTED ATTENTION. THE TH17/TREG BALANCE IS REGULATED BY INFLAMMATORY CYTOKINES AND VARIOUS METABOLIC FACTORS, INCLUDING THOSE ASSOCIATED WITH CELLULAR ENERGY METABOLISM. THE POSSIBLE UNDERLYING MECHANISMS INCLUDE METABOLISM-RELATED SIGNALING PATHWAYS AND EPIGENETIC REGULATION. SEVERAL STUDIES CONDUCTED ON HUMAN AND ANIMAL MODELS HAVE SHOWN MARKED DIFFERENCES IN AND THE IMPORTANT ROLES OF TH17/TREG IN CHRONIC INFLAMMATION ASSOCIATED WITH OBESITY AND METABOLIC DISEASES. MOREOVER, TH17/TREG SEEMS TO BE A BRIDGE LINKING THE GUT MICROBIOTA TO HOST METABOLIC DISORDERS. IN THIS REVIEW, WE HAVE PROVIDED AN OVERVIEW OF THE ALTERATIONS IN AND THE FUNCTIONS OF THE TH17/TREG BALANCE IN METABOLIC DISEASES AND ITS ROLE IN REGULATING IMMUNE RESPONSE-RELATED GLUCOSE AND LIPID METABOLISM. 2021 10 3539 26 IMMUNE SENESCENCE, EPIGENETICS AND AUTOIMMUNITY. AGING OF THE IMMUNE SYSTEM IN HUMANS AND ANIMALS IS CHARACTERIZED BY A DECLINE IN BOTH ADAPTIVE AND INNATE IMMUNE RESPONSES. PARADOXICALLY, AGING IS ALSO ASSOCIATED WITH A STATE OF CHRONIC INFLAMMATION ("INFLAMMAGING") AND AN INCREASED LIKELIHOOD OF DEVELOPING AUTOIMMUNE DISEASES. EPIGENETIC CHANGES IN NON-DIVIDING AND DIVIDING CELLS, INCLUDING IMMUNE CELLS, DUE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO THE INFLAMMATION AND AUTOIMMUNITY THAT CHARACTERIZE BOTH THE STATE AND DISEASES OF AGING. HERE, WE REVIEW THE EPIGENETIC MECHANISMS INVOLVED IN THE DEVELOPMENT OF IMMUNE SENESCENCE AND AUTOIMMUNITY IN OLD AGE. 2018 11 2591 36 EPIGENETICS OF PSORIASIS. PSORIASIS IS A CHRONIC AND RECURRENT INFLAMMATORY SKIN DISEASE, INVOLVING THE RAPID PROLIFERATION AND ABNORMAL DIFFERENTIATION OF KERATINOCYTES AND ACTIVATION OF T CELLS. IT IS GENERALLY ACCEPTED THAT THE CENTRAL PATHOGENESIS OF PSORIASIS IS A T CELL-DOMINANT IMMUNE DISORDER AFFECTED BY MULTIPLE FACTORS INCLUDING GENETIC SUSCEPTIBILITY, ENVIRONMENTAL FACTORS, INNATE AND ADAPTIVE IMMUNE RESPONSES, ETC. HOWEVER, THE EXACT ETIOLOGY IS LARGELY UNKNOWN. IN RECENT YEARS, EPIGENETIC INVOLVEMENTS, SUCH AS THE DNA METHYLATION, CHROMATIN MODIFICATIONS, AND NONCODING RNA REGULATION ARE REPORTED TO BE CRITICAL FOR THE PATHOGENESIS OF PSORIASIS. HOWEVER, THE INTERPLAY BETWEEN THESE FACTORS HAS ONLY RECENTLY BEEN STARTED TO BE UNRAVELED. NOTABLY, INHIBITORS OF ENZYMES THAT WORK IN EPIGENETIC MODIFICATIONS, SUCH AS DNA METHYLTRANSFERASES AND HISTONE DEACETYLASES, ARE BEGINNING TO APPEAR IN THE CLINICAL SETTING TO RESTORE NORMAL EPIGENETIC PATTERNS (GENERALI ET AL. IN J AUTOIMMUN 83:51-61, 2017), PROVIDING NOVEL THERAPEUTIC POTENTIAL AS NOVEL TREATMENT TARGETS FOR PSORIASIS. INDEED, MEDICATIONS PREVIOUSLY USED TO TREAT AUTOIMMUNE DISEASES HAVE LATER BEEN DISCOVERED TO EXERT THEIR ACTION VIA EPIGENETIC MECHANISMS. HEREIN, WE REVIEW THE FINDINGS ON EPIGENETICS ASSOCIATED WITH PSORIASIS, AND DISCUSS FUTURE PERSPECTIVES IN THIS FIELD. 2020 12 2501 32 EPIGENETICS AND ITS ROLE IN PERIODONTAL DISEASES: A STATE-OF-THE-ART REVIEW. THE IMMUNE RESPONSE TO ORAL BACTERIA AND THE SUBSEQUENT ACTIVATION OF INFLAMMATORY SIGNALING IS NOT ONLY DEPENDENT ON GENETIC FACTORS. THE IMPORTANCE OF SO-CALLED EPIGENETIC MECHANISMS PRESENTS ADDITIONAL REGULATORY PATHWAYS OF GENES INVOLVED IN MAINTAINING CHRONIC INFLAMMATION, INCLUDING GINGIVITIS AND PERIODONTITIS. THE TERM EPIGENETICS RELATES TO CHANGES IN GENE EXPRESSION THAT ARE NOT ENCODED IN THE DNA SEQUENCE ITSELF AND INCLUDE CHEMICAL ALTERATIONS OF DNA AND ITS ASSOCIATED PROTEINS. THESE CHANGES LEAD TO REMODELING OF THE CHROMATIN AND SUBSEQUENT ACTIVATION OR INACTIVATION OF A GENE. EPIGENETIC MECHANISMS HAVE BEEN FOUND TO CONTRIBUTE TO DISEASE, INCLUDING CANCER AND AUTOIMMUNE OR INFLAMMATORY DISEASES. IN THIS STATE-OF-THE ART REVIEW, THE AUTHORS PROVIDE THE LATEST FINDINGS ON THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS IN THE DEVELOPMENT OF PERIODONTAL DISEASE AND PRESENT EMERGING THERAPEUTIC STRATEGIES AIMED AT EPIGENETIC TARGETS (EPIDRUGS) ASSOCIATED WITH THE DISRUPTION OF TISSUE HOMEOSTASIS AND THE DEVELOPMENT OF PERIODONTITIS. 2015 13 2174 30 EPIGENETIC MECHANISMS INVOLVED IN MODULATION OF INFLAMMATORY DISEASES. PURPOSE OF REVIEW: THE ACTIVATION OF INFLAMMATORY RESPONSE IS DEPENDENT UPON GENETIC FACTORS AND EPIGENETIC CONTROL MECHANISMS. THIS OVERVIEW WILL HIGHLIGHT RECENT ADVANCES IN THE UNDERSTANDING OF EPIGENETIC DYNAMICS DURING CELLULAR INFLAMMATION. RECENT FINDINGS: THERE IS A GROWING BODY OF EVIDENCE INDICATING THAT ALTERATIONS OF THE CHROMATIN STATE ASSOCIATE WITH AN INCREASED RISK OF CHRONIC DISEASE DEVELOPMENT AND INFLAMMATION. EPIGENETIC ALTERATIONS RESPOND RAPIDLY TO ENVIRONMENTAL CHANGES AND HAVE A PROFOUND EFFECT ON GENE REGULATORY CROSS-WIRINGS AND TRANSCRIPTIONAL REGULATION. SUMMARY: SYSTEMATIC DISSECTION OF THE MECHANISMS UNDERLYING EPIGENETIC EFFECTS DURING INFLAMMATORY RESPONSE IS A CRITICAL STEP TOWARD ELUCIDATION OF THE CELL'S MOLECULAR PROCESSES AND HOLDS POTENTIAL FOR THE DEVELOPMENT OF NOVEL THERAPIES FOR THE TREATMENT OF CHRONIC DISEASES. 2016 14 6213 36 THE INTESTINAL EPITHELIAL CELL CYCLE: UNCOVERING ITS 'CRYPTIC' NATURE. PURPOSE OF REVIEW: TO DISCUSS THE RECENT LANDMARK FINDINGS THAT HAVE INCREASED OUR UNDERSTANDING NOT ONLY OF THE ROLE OF THE EPITHELIAL CELL CYCLE IN THE HOMEOSTASIS OF THE SMALL INTESTINE, BUT ALSO ITS RELEVANCE TO INFLAMMATION AND CANCER. RECENT FINDINGS: RECENT DATA HAVE UNVEILED NOVEL INFORMATION ON PROTEIN INTERACTIONS DIRECTLY INVOLVED IN THE CELL CYCLE AS WELL AS IN THE PATHWAYS THAT TRANSDUCE EXTERNAL ENVIRONMENTAL SIGNALS TO THE CELL CYCLE. A GROWING BODY OF THE RECENT EVIDENCE CONFIRMS THE IMPORTANCE OF FOOD AS WELL AS HORMONAL REGULATION IN THE GUT ON CELL CYCLE. INFORMATION ON THE CONTRIBUTION OF THE EPITHELIAL MICROENVIRONMENT, INCLUDING THE MICROBIOTA, HAS GROWN SUBSTANTIALLY IN THE RECENT YEARS AS WELL AS ON THE GENE-ENVIRONMENT INTERACTIONS AND THE MULTIPLE EPIGENETIC MECHANISMS INVOLVED IN REGULATING CELL-CYCLE PROTEINS AND SIGNALLING. FINALLY, FURTHER STUDIES INVESTIGATING THE DYSREGULATION OF THE CELL CYCLE DURING INFLAMMATION AND PROLIFERATION HAVE INCREASED OUR UNDERSTANDING OF THE PATHOPHYSIOLOGY OF CHRONIC INFLAMMATORY DISEASES AND CANCER. SUMMARY: THIS REVIEW HIGHLIGHTS SOME OF THE MOST RECENT ADVANCES THAT FURTHER EMPHASIZE THE IMPORTANCE OF THE CELL CYCLE IN THE SMALL INTESTINE DURING HOMEOSTASIS AS WELL AS IN INFLAMMATION AND CANCER. 2015 15 3703 26 INFLAMMATORY SIGNALLING AS MEDIATOR OF EPIGENETIC MODULATION IN TISSUE-SPECIFIC CHRONIC INFLAMMATION. RECENT SUCCESSES OF THERAPEUTIC INTERVENTION IN CHRONIC INFLAMMATORY DISEASES USING EPIGENETIC MODIFIERS SUCH AS HISTONE DEACETYLASE INHIBITORS AND INHIBITORS OF DNA METHYLATION SUGGEST THAT EPIGENETIC REPROGRAMMING PLAYS A ROLE IN THE AETIOLOGY OF THESE DISEASES. THE EPIGENETIC SIGNATURE OF A GIVEN IMMUNE CELL IS REFLECTED IN THE HISTORY OF MODIFICATIONS FROM DIFFERENT SIGNALS THE CELL HAS BEEN SUBJECTED TO DURING DIFFERENTIATION. LIKE OTHER CELLS, DIFFERENTIATING IMMUNE CELLS ARE DEPENDENT ON A COMPLEX COMBINATION OF INTER- AND INTRACELL SIGNALLING AS WELL AS TRANSCRIPTION MACHINERIES TO MODULATE THEIR EPIGENOMES IN ORDER TO MEDIATE DIFFERENTIATION. DESPITE EXTENSIVE RESEARCH INTO THESE PROCESSES, THE LINK BETWEEN CELLULAR SIGNALLING AND EPIGENETIC MODULATION REMAINS POORLY UNDERSTOOD. HERE, WE REVIEW RECENT PROGRESS AND DISCUSS KEY FACTORS DRIVING EPIGENETIC MODULATION IN CHRONIC INFLAMMATION. 2009 16 2601 42 EPIGENETICS, DNA ORGANIZATION, AND INFLAMMATORY BOWEL DISEASE. INFLAMMATORY BOWEL DISEASES (IBDS) ARE CHRONIC INFLAMMATORY DISORDERS AFFECTING THE GASTROINTESTINAL TRACT. THE INCIDENCE OF IBD IS INCREASING, WITH MORE CASES OCCURRING IN DEVELOPED COUNTRIES. MULTIPLE FACTORS SUCH AS GENETICS, ENVIRONMENTAL CHANGES, GUT MICROBIOTA, AND IMMUNE ABNORMALITIES HAVE BEEN ASSOCIATED WITH DEVELOPMENT OF IBD. IN RECENT YEARS, IT HAS BECOME INCREASINGLY APPARENT THAT EPIGENETIC MODIFICATIONS OF CHROMATIN AND THE MANNER IN WHICH CHROMATIN IS ORGANIZED IN THE NUCLEUS ARE ADDITIONALLY IMPORTANT ELEMENTS THAT CAN INFLUENCE RESPONSES INDUCED BY THE FACTORS DESCRIBED ABOVE, AND MAY THEREFORE CONTRIBUTE TO THE ONSET AND PATHOGENESIS OF IBD. EPIGENETICS AND CHROMATIN ORGANIZATION REGULATE DIVERSE FUNCTIONS THAT INCLUDE MAINTENANCE OF HOMEOSTASIS IN THE INTESTINAL EPITHELIUM, THE DEVELOPMENT AND DIFFERENTIATION OF IMMUNE CELLS, AND MODULATION OF RESPONSES GENERATED BY THE IMMUNE SYSTEM TO DEFEND AGAINST POTENTIAL PATHOGENS. FURTHERMORE, CHANGES IN EPIGENETIC CHROMATIN MARKS AND IN CHROMATIN ORGANIZATION HAVE NOW BEEN LINKED TO DIFFERENTIAL GENE EXPRESSION IN IBD PATIENT CELLS. ALTHOUGH DIRECT EVIDENCE FOR A ROLE OF HISTONE MODIFICATIONS IN IBD IS CURRENTLY VERY LIMITED, IN THIS REVIEW, WE SUMMARIZE THE LINKS BETWEEN VARIOUS EPIGENETIC MODIFICATIONS, THE PROTEINS THAT CATALYZE OR RECOGNIZE THESE MODIFICATIONS, AND THE DEVELOPMENT OR PROGRESSION OF IBD IN HUMAN AND EXPERIMENTAL IBD. WE ALSO DISCUSS HOW EPIGENETICS INFLUENCE THE ORGANIZATION OF DNA CONTACTS TO REGULATE GENE EXPRESSION AND THE IMPLICATIONS THIS MAY HAVE FOR DIAGNOSING AND TREATING IBD. 2019 17 2333 29 EPIGENETIC REGULATION OF INFLAMMATION: THE METABOLOMICS CONNECTION. EPIGENETIC FACTORS ARE CONSIDERED THE REGULATOR OF COMPLEX MACHINERY BEHIND INFLAMMATORY DISORDERS AND SIGNIFICANTLY CONTRIBUTED TO THE EXPRESSION OF INFLAMMATION-ASSOCIATED GENES. EPIGENETIC MODIFICATIONS MODULATE VARIATION IN THE EXPRESSION PATTERN OF TARGET GENES WITHOUT AFFECTING THE DNA SEQUENCE. THE CURRENT KNOWLEDGE OF EPIGENETIC RESEARCH FOCUSED ON THEIR ROLE IN THE PATHOGENESIS OF VARIOUS INFLAMMATORY DISEASES THAT CAUSES MORBIDITY AND MORTALITY WORLDWIDE. INFLAMMATORY DISEASES ARE CATEGORIZED AS ACUTE AND CHRONIC BASED ON THE DISEASE SEVERITY AND ARE REGULATED BY THE EXPRESSION PATTERN OF VARIOUS GENES. HENCE, UNDERSTANDING THE ROLE OF EPIGENETIC MODIFICATIONS DURING INFLAMMATION PROGRESSION WILL CONTRIBUTE TO THE DISEASE OUTCOMES AND THERAPEUTIC APPROACHES. THIS REVIEW ALSO FOCUSES ON THE METABOLOMICS APPROACH ASSOCIATED WITH THE STUDY OF INFLAMMATORY DISORDERS. INFLAMMATORY RESPONSES AND METABOLIC REGULATION ARE HIGHLY INTEGRATED AND VARIOUS ADVANCED TECHNIQUES ARE ADOPTED TO STUDY THE METABOLIC SIGNATURE MOLECULES. HERE WE DISCUSS SEVERAL METABOLOMICS APPROACHES USED TO LINK INFLAMMATORY DISORDERS AND EPIGENETIC CHANGES. WE PROPOSED THAT DECIPHERING THE MECHANISM BEHIND THE INFLAMMATION-METABOLISM LOOP MAY HAVE IMMENSE IMPORTANCE IN BIOMARKERS RESEARCH AND MAY ACT AS A PRINCIPAL COMPONENT IN DRUG DISCOVERY AS WELL AS THERAPEUTIC APPLICATIONS. 2022 18 2338 28 EPIGENETIC REGULATION OF INFLAMMATORY SIGNALING AND INFLAMMATION-INDUCED CANCER. EPIGENETICS COMPRISE A DIVERSE ARRAY OF REVERSIBLE AND DYNAMIC MODIFICATIONS TO THE CELL'S GENOME WITHOUT IMPLICATING ANY DNA SEQUENCE ALTERATIONS. BOTH THE EXTERNAL ENVIRONMENT SURROUNDING THE ORGANISM, AS WELL AS THE INTERNAL MICROENVIRONMENT OF CELLS AND TISSUES, CONTRIBUTE TO THESE EPIGENETIC PROCESSES THAT PLAY CRITICAL ROLES IN CELL FATE SPECIFICATION AND ORGANISMAL DEVELOPMENT. ON THE OTHER HAND, DYSREGULATION OF EPIGENETIC ACTIVITIES CAN INITIATE AND SUSTAIN CARCINOGENESIS, WHICH IS OFTEN AUGMENTED BY INFLAMMATION. CHRONIC INFLAMMATION, ONE OF THE MAJOR HALLMARKS OF CANCER, STEMS FROM PROINFLAMMATORY CYTOKINES THAT ARE SECRETED BY TUMOR AND TUMOR-ASSOCIATED CELLS IN THE TUMOR MICROENVIRONMENT. AT THE SAME TIME, INFLAMMATORY SIGNALING CAN ESTABLISH POSITIVE AND NEGATIVE FEEDBACK CIRCUITS WITH CHROMATIN TO MODULATE CHANGES IN THE GLOBAL EPIGENETIC LANDSCAPE. IN THIS REVIEW, WE PROVIDE AN IN-DEPTH DISCUSSION OF THE INTERCONNECTED CROSSTALK BETWEEN EPIGENETICS AND INFLAMMATION, SPECIFICALLY HOW EPIGENETIC MECHANISMS AT DIFFERENT HIERARCHICAL LEVELS OF THE GENOME CONTROL INFLAMMATORY GENE TRANSCRIPTION, WHICH IN TURN ENACT CHANGES WITHIN THE CELL'S EPIGENOMIC PROFILE, ESPECIALLY IN THE CONTEXT OF INFLAMMATION-INDUCED CANCER. 2022 19 6101 19 THE EMERGING ROLE OF EPIGENETICS IN THE IMMUNE RESPONSE TO VACCINATION AND INFECTION: A SYSTEMATIC REVIEW. EXTENSIVE RESEARCH HAS HIGHLIGHTED THE ROLE OF INFECTION-INDUCED EPIGENETIC EVENTS IN THE DEVELOPMENT OF CANCER. MORE RECENTLY, ATTENTION HAS FOCUSED ON THE ABILITY OF NON-CARCINOGENIC INFECTIONS, AS WELL AS VACCINES, TO MODIFY THE HUMAN EPIGENOME AND MODULATE THE IMMUNE RESPONSE. THIS REVIEW EXPLORES THIS RAPIDLY EVOLVING AREA OF INVESTIGATION AND OUTLINES THE MANY AND VARIED WAYS IN WHICH VACCINATION AND NATURAL INFECTION CAN INFLUENCE THE HUMAN EPIGENOME FROM MODULATION OF THE INNATE AND ADAPTIVE IMMUNE RESPONSE, TO BIOLOGICAL AGEING AND MODIFICATION OF DISEASE RISK. THE IMPLICATIONS OF THESE EPIGENETIC CHANGES ON IMMUNE REGULATION AND THEIR POTENTIAL APPLICATION TO THE DIAGNOSIS AND TREATMENT OF CHRONIC INFECTION AND VACCINE DEVELOPMENT ARE ALSO DISCUSSED. 2020 20 6136 33 THE EPIGENETICS OF MULTIPLE SCLEROSIS AND OTHER RELATED DISORDERS. MULTIPLE SCLEROSIS (MS) IS A DEMYELINATING DISEASE CHARACTERIZED BY CHRONIC INFLAMMATION OF THE CENTRAL NERVOUS SYSTEM (CNS) GRAY AND WHITE MATTER. ALTHOUGH THE CAUSE OF MS IS UNKNOWN, IT IS WIDELY APPRECIATED THAT INNATE AND ADAPTIVE IMMUNE PROCESSES CONTRIBUTE TO ITS PATHOGENESIS. THESE INCLUDE MICROGLIA/MACROPHAGE ACTIVATION, PRO-INFLAMMATORY T-CELL (TH1) RESPONSES AND HUMORAL RESPONSES. ADDITIONALLY, THERE IS EVIDENCE INDICATING THAT MS HAS A NEURODEGENERATIVE COMPONENT SINCE NEURONAL AND AXONAL LOSS OCCURS EVEN IN THE ABSENCE OF OVERT INFLAMMATION. THESE ASPECTS ALSO FORM THE RATIONALE FOR CLINICAL MANAGEMENT OF THE DISEASE. HOWEVER, THE CURRENTLY AVAILABLE THERAPIES TO CONTROL THE DISEASE ARE ONLY PARTIALLY EFFECTIVE AT BEST INDICATING THAT MORE EFFECTIVE THERAPEUTIC SOLUTIONS ARE URGENTLY NEEDED. IT IS APPRECIATED THAT IN THE IMMUNE-DRIVEN AND NEURODEGENERATIVE PROCESSES MS-SPECIFIC DEREGULATION OF GENE EXPRESSIONS AND RESULTING PROTEIN DYSFUNCTION ARE THOUGHT TO PLAY A CENTRAL ROLE. THESE DEVIATIONS IN GENE EXPRESSION PATTERNS CONTRIBUTE TO THE INFLAMMATORY RESPONSE IN THE CNS, AND TO NEURONAL OR AXONAL LOSS. EPIGENETIC MECHANISMS CONTROL TRANSCRIPTION OF MOST, IF NOT ALL GENES, IN NUCLEATED CELLS INCLUDING CELLS OF THE CNS AND IN HAEMATOPOIETIC CELLS. MS-SPECIFIC ALTERATIONS IN EPIGENETIC REGULATION OF GENE EXPRESSION MAY THEREFORE LIE AT THE HEART OF THE DEREGULATION OF GENE EXPRESSION IN MS. AS SUCH, EPIGENETIC MECHANISMS MOST LIKELY PLAY AN IMPORTANT ROLE IN DISEASE PATHOGENESIS. IN THIS REVIEW WE DISCUSS A ROLE FOR MS-SPECIFIC DEREGULATION OF EPIGENETIC FEATURES THAT CONTROL GENE EXPRESSION IN THE CNS AND IN THE PERIPHERY. FURTHERMORE, WE DISCUSS THE APPLICATION OF SMALL MOLECULE INHIBITORS THAT TARGET THE EPIGENETIC MACHINERY TO AMELIORATE DISEASE IN EXPERIMENTAL ANIMAL MODELS, INDICATING THAT SUCH APPROACHES MAY BE APPLICABLE TO MS PATIENTS. 2014