1 1208 123 COVID-19 INFECTION AND RESPONSE TO VACCINATION IN CHRONIC KIDNEY DISEASE AND RENAL TRANSPLANTATION: A BRIEF PRESENTATION. CHRONIC KIDNEY DISEASE (CKD) IS ASSOCIATED WITH PHENOTYPIC AND FUNCTIONAL CHANGES IN THE IMMUNE SYSTEM, FOLLOWED BY DETRIMENTAL CLINICAL CONSEQUENCES, SUCH AS SEVERE INFECTIONS AND DEFECTIVE RESPONSE TO VACCINATION. TWO YEARS OF THE PANDEMIC, DUE TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2), HAVE UNDOUBTEDLY CHANGED THE WORLD; HOWEVER, ALL EFFORTS TO CONFRONT INFECTION AND PROVIDE NEW GENERATION VACCINES TREMENDOUSLY IMPROVED OUR UNDERSTANDING OF THE MECHANISMS OF THE IMMUNE RESPONSE AGAINST INFECTIONS AND AFTER VACCINATION. HUMORAL AND CELLULAR RESPONSES TO VACCINES, INCLUDING MRNA VACCINES, ARE APPARENTLY AFFECTED IN CKD PATIENTS, AS ELIMINATION OF RECENT THYMIC EMIGRANT AND NAIVE LYMPHOCYTES AND REGULATORY T-CELLS, TOGETHER WITH CONTRACTION OF T-CELL REPERTOIRE AND HOMEOSTATIC PROLIFERATION RATE, WHICH CHARACTERIZED CKD PATIENTS ARE RESPONSIBLE FOR IMPAIRED IMMUNE ACTIVATION. SUCCESSFUL RENAL TRANSPLANTATION WILL RESTORE SOME OF THESE CHANGES, ALTHOUGH SEVERAL EPIGENETIC CHANGES ARE IRREVERSIBLE AND EVEN ACCELERATED BY THE INDUCTION OF IMMUNOSUPPRESSION. RESPONSE TO VACCINATION IS DEFINITELY IMPAIRED AMONG BOTH CKD AND RT PATIENTS. IN THE PRESENT REVIEW, WE ANALYZED THE DIFFERENCES IN IMMUNE RESPONSE AFTER VACCINATION BETWEEN THESE PATIENTS AND HEALTHY INDIVIDUALS AND DEPICTED SPECIFIC PARAMETERS, SUCH AS ALTERATIONS IN THE IMMUNE SYSTEM, PREDISPOSING TO THIS DEFICIENT RESPONSE. 2022 2 5618 26 SARS-COV-2 INTERACTION WITH HUMAN DNA METHYL TRANSFERASE 1: A POTENTIAL RISK FOR INCREASING THE INCIDENCE OF LATER CHRONIC DISEASES IN THE SURVIVED PATIENTS. CURRENTLY, THE COVID-19 PANDEMIC IS THE MOST DISCUSSED SUBJECT IN MEDICAL RESEARCHES WORLDWIDE. AS THE KNOWLEDGE IS EXPANDED ABOUT THE DISEASE, MORE HYPOTHESES BECOME CREATED. A RECENT STUDY ON THE VIRAL PROTEIN INTERACTION MAP REVEALED THAT SARS-COV-2 OPEN READING FRAME 8 (ORF8) INTERACTS WITH HUMAN DNA METHYL TRANSFERASE1 (DNMT1), AN ACTIVE EPIGENETIC AGENT IN DNA METHYLATION. MOREOVER, DNMT1 IS A CONTRIBUTOR TO A VARIETY OF CHRONIC DISEASES WHICH COULD CAUSE SOME EPIGENETIC DYSREGULATION IN INFECTED CELLS, ESPECIALLY LEUKOCYTES, PANCREATIC BETA, AND ENDOTHELIAL CELLS. REGARDING THE FACT THAT EPIGENETIC ALTERATIONS HAVE A PARTIAL, BUT NOT COMPLETELY REVERSIBLE PHENOMENA, IT RAISES THE QUESTION THAT IF THIS INTERACTION MAY CAUSE LONG-TERM COMPLICATIONS SUCH AS DIABETES, ATHEROSCLEROSIS, CANCER, AND AUTOIMMUNE DISEASES. ACCORDINGLY, LONG FOLLOW-UP STUDIES ON THE RECOVERED PATIENTS FROM COVID-19 ARE RECOMMENDED. 2022 3 1604 33 DNA METHYLATION SUSTAINS "INFLAMED" MEMORY OF PERIPHERAL IMMUNE CELLS AGGRAVATING KIDNEY INFLAMMATORY RESPONSE IN CHRONIC KIDNEY DISEASE. THE INCIDENCE OF CHRONIC KIDNEY DISEASE (CKD) HAS RAPIDLY INCREASED IN THE PAST DECADES. A PROGRESSIVE LOSS OF KIDNEY FUNCTION CHARACTERIZES A PART OF CKD EVEN WITH INTENSIVE SUPPORTIVE TREATMENT. IRRESPECTIVE OF ITS ETIOLOGY, CKD PROGRESSION IS GENERALLY ACCOMPANIED WITH THE DEVELOPMENT OF CHRONIC KIDNEY INFLAMMATION THAT IS PATHOLOGICALLY FEATURED BY THE LOW-GRADE BUT CHRONIC ACTIVATION OF RECRUITED IMMUNE CELLS. CUMULATIVE EVIDENCE SUPPORT THAT ABERRANT DNA METHYLATION PATTERN OF DIVERSE PERIPHERAL IMMUNE CELLS, INCLUDING T CELLS AND MONOCYTES, IS CLOSELY ASSOCIATED WITH CKD DEVELOPMENT IN MANY CHRONIC DISEASE SETTINGS. THE CHANGE OF DNA METHYLATION PROFILE CAN SUSTAIN FOR A LONG TIME AND AFFECT THE FUTURE GENES EXPRESSION IN THE CIRCULATING IMMUNE CELLS EVEN AFTER THEY MIGRATE FROM THE CIRCULATION INTO THE INVOLVED KIDNEY. IT IS OF CLINICAL INTEREST TO REVEAL THE UNDERLYING MECHANISM OF HOW ALTERED DNA METHYLATION REGULATES THE INTENSITY AND THE TIME LENGTH OF THE INFLAMMATORY RESPONSE IN THE RECRUITED EFFECTOR CELLS. WE AND OTHERS RECENTLY DEMONSTRATED THAT ALTERED DNA METHYLATION OCCURS IN PERIPHERAL IMMUNE CELLS AND PROFOUNDLY CONTRIBUTES TO CKD DEVELOPMENT IN SYSTEMIC CHRONIC DISEASES, SUCH AS DIABETES AND HYPERTENSION. THIS REVIEW WILL SUMMARIZE THE CURRENT FINDINGS ABOUT THE INFLUENCE OF ABERRANT DNA METHYLATION ON CIRCULATING IMMUNE CELLS AND HOW IT POTENTIALLY DETERMINES THE OUTCOME OF CKD. 2021 4 5135 40 POTENTIAL MECHANISMS FOR LUNG FIBROSIS ASSOCIATED WITH COVID-19 INFECTION. PULMONARY FIBROSIS IS A SEQUELAE OF SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION THAT CURRENTLY LACKS EFFECTIVE PREVENTATIVE OR THERAPEUTIC MEASURES. POST-VIRAL LUNG FIBROSIS DUE TO SARS-COV-2 HAS BEEN SHOWN TO BE PROGRESSIVE ON SELECTED PATIENTS USING IMAGING STUDIES. PERSISTENT INFILTRATION OF MACROPHAGES AND MONOCYTES, A MAIN FEATURE OF SARS-COV-2 PULMONARY FIBROSIS, AND LONG-LIVED CIRCULATING INFLAMMATORY MONOCYTES MIGHT BE DRIVING FACTORS PROMOTING THE PROFIBROTIC MILIEU IN THE LUNG. THE UPSTREAM SIGNAL(S) THAT REGULATES THE PRESENCE OF THESE IMMUNE CELLS (DESPITE COMPLETE VIRAL CLEARANCE) REMAINS TO BE EXPLORED. CURRENT DATA INDICATE THAT MUCH OF THE STIMULATING SIGNALS ARE LOCALIZED IN THE LUNGS. HOWEVER, AN ONGOING LOW-GRADE SYSTEMIC INFLAMMATION IN LONG CORONAVIRUS DISEASE 2019 (COVID-19) SYMPTOMS SUGGESTS THAT CERTAIN NON-PULMONARY REGULATORS SUCH AS EPIGENETIC CHANGES IN HEMATOPOIETIC STEM CELLS MIGHT BE CRITICAL TO THE CHRONIC INFLAMMATORY RESPONSE. SINCE NEARLY ONE-THIRD OF THE WORLD POPULATION HAVE BEEN INFECTED, A TIMELY UNDERSTANDING OF THE UNDERLYING PATHOGENESIS LEADING TO TISSUE REMODELING IS REQUIRED. HEREIN, WE REVIEW THE POTENTIAL PATHOGENIC MECHANISMS DRIVING LUNG FIBROSIS FOLLOWING SARS-COV-2 INFECTION BASED UPON AVAILABLE STUDIES AND OUR PRELIMINARY FINDINGS (GRAPHICAL ABSTRACT). 2023 5 6101 21 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 6 727 39 CAN VITAMINS, AS EPIGENETIC MODIFIERS, ENHANCE IMMUNITY IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASE? PURPOSE OF REVIEW: THE HIGHLY INFECTIOUS TRANSMISSIBLE DISEASE, THE NOVEL SARS-COV-2, CAUSING THE CORONAVIRUS DISEASE (COVID-19), HAS A MEDIAN INCUBATION TIME OF 5 TO 15 DAYS. THE SYMPTOMS VARY FROM PERSON TO PERSON AND MANY ARE "HIDDEN CARRIERS." FEW PEOPLE EXPERIENCE IMMEDIATE REACTION AND EVEN DEATH WITHIN 48 H OF INFECTION. HOWEVER, MANY SHOW MILD TO CHRONIC SYMPTOMS AND RECOVER. NEVERTHELESS, THE DEATH RATE DUE TO COVID-19 TRANSMISSION IS HIGH ESPECIALLY AMONG PATIENTS WITH NON-COMMUNICABLE DISEASES. THE PURPOSE OF THIS REVIEW IS TO PROVIDE EVIDENCE TO CONSIDER VITAMINS AS EPIGENETIC MODIFIERS TO ENHANCE IMMUNITY AND REDUCE INFLAMMATORY RESPONSE IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASES. RECENT FINDINGS: CLINICAL EVIDENCE HAS SUGGESTED THE RISK OF GETTING INFECTED IS HIGH AMONG INDIVIDUALS WITH NON-COMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASE, TYPE-2 DIABETES, CANCER, ACUTE RESPIRATORY DISTRESS SYNDROME, AND RENAL DISEASE, AS WELL AS THE ELDERLY WITH HIGH MORTALITY RATE AMONG THE COHORT. THE IMPACT IS DUE TO AN ALREADY COMPROMISED IMMUNE SYSTEM OF PATIENTS. EVERY PATIENT HAS A DIFFERENT RESPONSE TO COVID-19, WHICH SHOWS THAT THE ABILITY TO COMBAT THE DEADLY VIRUS VARIES INDIVIDUALLY. THUS, TREATMENT CAN BE PERSONALIZED AND ADJUSTED TO HELP PROTECT AND COMBAT COVID-19 INFECTIONS, ESPECIALLY IN INDIVIDUALS WITH NON-COMMUNICABLE DISEASES. BASED ON CURRENT PUBLISHED SCIENTIFIC AND MEDICAL EVIDENCE, THE SUGGESTIONS MADE IN THIS ARTICLE FOR COMBINATION OF VITAMIN THERAPY AS EPIGENETIC MODIFIERS TO CONTROL THE UNREGULATED INFLAMMATORY AND CYTOKINE MARKER EXPRESSIONS, FURTHER NEEDS TO BE CLINICALLY PROVEN. FUTURE RESEARCH AND CLINICAL TRIALS CAN APPLY THE SUGGESTIONS GIVEN IN THIS ARTICLE TO SUPPORT METABOLIC ACTIVITIES IN PATIENTS AND ENHANCE THE IMMUNE RESPONSE. 2020 7 3551 33 IMMUNOSENESCENCE: MOLECULAR MECHANISMS AND DISEASES. INFECTION SUSCEPTIBILITY, POOR VACCINATION EFFICACY, AGE-RELATED DISEASE ONSET, AND NEOPLASMS ARE LINKED TO INNATE AND ADAPTIVE IMMUNE DYSFUNCTION THAT ACCOMPANIES AGING (KNOWN AS IMMUNOSENESCENCE). DURING AGING, ORGANISMS TEND TO DEVELOP A CHARACTERISTIC INFLAMMATORY STATE THAT EXPRESSES HIGH LEVELS OF PRO-INFLAMMATORY MARKERS, TERMED INFLAMMAGING. THIS CHRONIC INFLAMMATION IS A TYPICAL PHENOMENON LINKED TO IMMUNOSENESCENCE AND IT IS CONSIDERED THE MAJOR RISK FACTOR FOR AGE-RELATED DISEASES. THYMIC INVOLUTION, NAIVE/MEMORY CELL RATIO IMBALANCE, DYSREGULATED METABOLISM, AND EPIGENETIC ALTERATIONS ARE STRIKING FEATURES OF IMMUNOSENESCENCE. DISTURBED T-CELL POOLS AND CHRONIC ANTIGEN STIMULATION MEDIATE PREMATURE SENESCENCE OF IMMUNE CELLS, AND SENESCENT IMMUNE CELLS DEVELOP A PROINFLAMMATORY SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE THAT EXACERBATES INFLAMMAGING. ALTHOUGH THE UNDERLYING MOLECULAR MECHANISMS REMAIN TO BE ADDRESSED, IT IS WELL DOCUMENTED THAT SENESCENT T CELLS AND INFLAMMAGING MIGHT BE MAJOR DRIVING FORCES IN IMMUNOSENESCENCE. POTENTIAL COUNTERACTIVE MEASURES WILL BE DISCUSSED, INCLUDING INTERVENTION OF CELLULAR SENESCENCE AND METABOLIC-EPIGENETIC AXES TO MITIGATE IMMUNOSENESCENCE. IN RECENT YEARS, IMMUNOSENESCENCE HAS ATTRACTED INCREASING ATTENTION FOR ITS ROLE IN TUMOR DEVELOPMENT. AS A RESULT OF THE LIMITED PARTICIPATION OF ELDERLY PATIENTS, THE IMPACT OF IMMUNOSENESCENCE ON CANCER IMMUNOTHERAPY IS UNCLEAR. DESPITE SOME SURPRISING RESULTS FROM CLINICAL TRIALS AND DRUGS, IT IS NECESSARY TO INVESTIGATE THE ROLE OF IMMUNOSENESCENCE IN CANCER AND OTHER AGE-RELATED DISEASES. 2023 8 551 34 AUTOIMMUNITY AS AN ETIOLOGICAL FACTOR OF CANCER: THE TRANSFORMATIVE POTENTIAL OF CHRONIC TYPE 2 INFLAMMATION. RECENT EPIDEMIOLOGICAL STUDIES HAVE FOUND AN ALARMING TREND OF INCREASED CANCER INCIDENCE IN ADULTS YOUNGER THAN 50 YEARS OF AGE AND PROJECTED A SUBSTANTIAL RISE IN CANCER INCIDENCE OVER THE NEXT 10 YEARS IN THIS AGE GROUP. THIS TREND WAS EXEMPLIFIED IN THE INCIDENCE OF NON-CARDIA GASTRIC CANCER AND ITS DISPROPORTIONATE IMPACT ON NON-HISPANIC WHITE FEMALES UNDER THE AGE OF 50. THE TREND IS CONCURRENT WITH THE INCREASING INCIDENCE OF AUTOIMMUNE DISEASES IN INDUSTRIALIZED COUNTRIES, SUGGESTING A CAUSAL LINK BETWEEN THE TWO. WHILE AUTOIMMUNITY HAS BEEN SUSPECTED TO BE A RISK FACTOR FOR SOME CANCERS, THE EXACT MECHANISMS UNDERLYING THE CONNECTION BETWEEN AUTOIMMUNITY AND CANCER REMAIN UNCLEAR AND ARE OFTEN CONTROVERSIAL. THE LINK HAS BEEN ATTRIBUTED TO SEVERAL MEDIATORS SUCH AS IMMUNE SUPPRESSION, INFECTION, DIET, ENVIRONMENT, OR, PERHAPS MOST PLAUSIBLY, CHRONIC INFLAMMATION BECAUSE OF ITS WELL-RECOGNIZED ROLE IN TUMORIGENESIS. IN THAT REGARD, AUTOIMMUNE CONDITIONS ARE COMMON CAUSES OF CHRONIC INFLAMMATION AND MAY TRIGGER REPETITIVE CYCLES OF ANTIGEN-SPECIFIC CELL DAMAGE, TISSUE REGENERATION, AND WOUND HEALING. ILLUSTRATING THE CONNECTION BETWEEN AUTOIMMUNE DISEASES AND CANCER ARE PATIENTS WHO HAVE AN INCREASED RISK OF CANCER DEVELOPMENT ASSOCIATED WITH GENETICALLY PREDISPOSED INSUFFICIENCY OF CYTOTOXIC T LYMPHOCYTE-ASSOCIATED PROTEIN 4 (CTLA4), A PROTOTYPICAL IMMUNE CHECKPOINT AGAINST AUTOIMMUNITY AND ONE OF THE MAIN TARGETS OF CANCER IMMUNE THERAPY. THE TUMORIGENIC PROCESS TRIGGERED BY CTLA4 INSUFFICIENCY HAS BEEN SHOWN IN A MOUSE MODEL TO BE DEPENDENT ON THE TYPE 2 CYTOKINES INTERLEUKIN-4 (IL4) AND INTERLEUKIN-13 (IL13). IN THIS TYPE 2 INFLAMMATORY MILIEU, CROSSTALK WITH TYPE 2 IMMUNE CELLS MAY INITIATE EPIGENETIC REPROGRAMMING OF EPITHELIAL CELLS, LEADING TO A METAPLASTIC DIFFERENTIATION AND EVENTUALLY MALIGNANT TRANSFORMATION EVEN IN THE ABSENCE OF CLASSICAL ONCOGENIC MUTATIONS. THOSE FINDINGS COMPLEMENT A LARGE BODY OF EVIDENCE FOR TYPE 1, TYPE 3, OR OTHER INFLAMMATORY MEDIATORS IN INFLAMMATORY TUMORIGENESIS. THIS REVIEW ADDRESSES THE POTENTIAL OF AUTOIMMUNITY AS A CAUSAL FACTOR FOR TUMORIGENESIS, THE UNDERLYING INFLAMMATORY MECHANISMS THAT MAY VARY DEPENDING ON HOST-ENVIRONMENT VARIATIONS, AND IMPLICATIONS TO CANCER PREVENTION AND IMMUNOTHERAPY. 2021 9 3549 34 IMMUNOSENESCENCE AND MULTIPLE SCLEROSIS. CHANGES IN THE IMMUNE SYSTEM ASSOCIATED WITH AGEING ARE KNOWN AS IMMUNOSENESCENCE. THIS IS CHARACTERISED BY A DECLINE IN IMMUNE RESPONSE, CHRONIC INFLAMMATION AND AN INCREASED RISK OF AUTOIMMUNE DISEASES. A CHRONIC INFLAMMATORY PROCESS WITH PERSISTENT PRODUCTION OF PROINFLAMMATORY MEDIATORS INCREASES THE RISK FOR MORBIDITY AND MORTALITY RELATED TO AGE, AND HAS BEEN DUBBED 'INFLAMM-AGEING'. IMMUNOSENESCENCE IS ASSOCIATED WITH A DECREASE IN THE NUMBER OF NAIVE T AND B CELLS, NK CELLS AND DISRUPTION OF THE PRO- AND ANTI-INFLAMMATORY BALANCE BY CHANGES IN THE PRODUCTION OF CYTOKINES. IN FACT, AGEING OF THE IMMUNE SYSTEM HAS A COMPLEX NETWORK OF UNDERLYING CAUSES WHICH INCLUDE NOT ONLY NATURAL MECHANISMS OF SENESCENCE BUT ALSO CHRONIC DISORDERS, LIFESTYLE, ENVIRONMENTAL AND EPIGENETIC FACTORS, AND INFECTIONS. MOREOVER, IMMUNOSENESCENCE HAS AN INFLUENCE ON THE COURSE OF CHRONIC DISEASES WHICH HAVE AN ONSET IN YOUNG ADULTS, SUCH AS MULTIPLE SCLEROSIS (MS). CURRENT DISEASE MODIFYING THERAPIES (DMTS) IN MS AIM TO REDUCE THE FREQUENCY OF RELAPSES AND TO SLOW DISEASE PROGRESSION, BUT THEY DO NOT NECESSARILY STOP THE ACCUMULATION OF DISABILITY RELATED TO DISEASE PROGRESSION. SOME FEATURES OF IMMUNOSENESCENCE FOUND IN AGED HEALTHY CONTROLS ARE ALREADY OBSERVED IN MS PATIENTS AT A YOUNGER AGE. THE OLDER POPULATION IS CHARACTERISED BY AN INCREASED SUSCEPTIBILITY TO INFECTIONS, A POOR RESPONSE TO VACCINATIONS, AND A HIGHER RISK OF DEVELOPING CANCER, VASCULAR DISEASES AND NEURODEGENERATION. IMMUNOSENESCENCE IS AN IMPORTANT FACTOR INFLUENCING THE COURSE OF MS, AND THE SAFETY AND EFFECTIVENESS OF DMTS. THE RELATIONSHIP BETWEEN THE PATHOGENIC PROCESS UNDERLYING THE DEVELOPMENT OF MS AND IMMUNOSENESCENCE REQUIRES FURTHER INVESTIGATION. 2022 10 4043 27 MACROPHAGES IN CHRONIC LIVER FAILURE: DIVERSITY, PLASTICITY AND THERAPEUTIC TARGETING. CHRONIC LIVER INJURY RESULTS IN IMMUNE-DRIVEN PROGRESSIVE FIBROSIS, WITH RISK OF CIRRHOSIS DEVELOPMENT AND IMPACT ON MORBIDITY AND MORTALITY. PERSISTENT LIVER CELL DAMAGE AND DEATH CAUSES IMMUNE CELL ACTIVATION AND INFLAMMATION. PATIENTS WITH ADVANCED CIRRHOSIS ADDITIONALLY EXPERIENCE PATHOLOGICAL BACTERIAL TRANSLOCATION, EXPOSURE TO MICROBIAL PRODUCTS AND CHRONIC ENGAGEMENT OF THE IMMUNE SYSTEM. BACTERIAL INFECTIONS HAVE A HIGH INCIDENCE IN CIRRHOSIS, WITH SPONTANEOUS BACTERIAL PERITONITIS BEING THE MOST COMMON, WHILE THE SUBSEQUENT SYSTEMIC INFLAMMATION, ORGAN FAILURE AND IMMUNE DYSREGULATION INCREASE THE MORTALITY RISK. TISSUE-RESIDENT AND RECRUITED MACROPHAGES PLAY A CENTRAL PART IN THE DEVELOPMENT OF INFLAMMATION AND FIBROSIS PROGRESSION. IN THE LIVER, ADIPOSE TISSUE, PERITONEUM AND INTESTINES, DIVERSE MACROPHAGE POPULATIONS EXHIBIT GREAT PHENOTYPIC AND FUNCTIONAL PLASTICITY DETERMINED BY THEIR ONTOGENY, EPIGENETIC PROGRAMMING AND LOCAL MICROENVIRONMENT. THESE CHANGES CAN, AT DIFFERENT TIMES, PROMOTE OR AMELIORATE DISEASE STATES AND THEREFORE REPRESENT POTENTIAL TARGETS FOR MACROPHAGE-DIRECTED THERAPIES. IN THIS REVIEW, WE DISCUSS THE EVIDENCE FOR MACROPHAGE PHENOTYPIC AND FUNCTIONAL ALTERATIONS IN TISSUE COMPARTMENTS DURING THE DEVELOPMENT AND PROGRESSION OF CHRONIC LIVER FAILURE IN DIFFERENT AETIOLOGIES AND HIGHLIGHT THE POTENTIAL OF MACROPHAGE MODULATION AS A THERAPEUTIC STRATEGY FOR LIVER DISEASE. 2021 11 4200 44 METABOLIC REQUIREMENTS OF TH17 CELLS AND OF B CELLS: REGULATION AND DEFECTS IN HEALTH AND IN INFLAMMATORY DISEASES. THE IMMUNE SYSTEM PROTECTS FROM INFECTIONS AND CANCER THROUGH COMPLEX CELLULAR NETWORKS. FOR THIS PURPOSE, IMMUNE CELLS REQUIRE WELL-DEVELOPED MECHANISMS OF ENERGY GENERATION. HOWEVER, THE IMMUNE SYSTEM ITSELF CAN ALSO CAUSE DISEASES WHEN DEFECTIVE REGULATION RESULTS IN THE EMERGENCE OF AUTOREACTIVE LYMPHOCYTES. RECENT STUDIES PROVIDE INSIGHTS INTO HOW DIFFERENTIAL PATTERNS OF IMMUNE CELL RESPONSES ARE ASSOCIATED WITH SELECTIVE METABOLIC PATHWAYS. THIS REVIEW WILL EXAMINE THE CHANGING METABOLIC REQUIREMENTS OF TH17 CELLS AND OF B CELLS AT DIFFERENT STAGES OF THEIR DEVELOPMENT AND ACTIVATION. BOTH CELLS PROVIDE PROTECTION BUT CAN ALSO MEDIATE DISEASES THROUGH THE PRODUCTION OF AUTOANTIBODIES AND THE PRODUCTION OF PROINFLAMMATORY MEDIATORS. IN HEALTH, B CELLS PRODUCE ANTIBODIES AND CYTOKINES AND PRESENT ANTIGENS TO T CELLS TO MOUNT SPECIFIC IMMUNITY. TH17 CELLS, ON THE OTHER HAND, PROVIDE PROTECTION AGAINST EXTRA CELLULAR PATHOGENS AT MUCOSAL SURFACES BUT CAN ALSO DRIVE CHRONIC INFLAMMATION. THE LATTER CELLS CAN ALSO PROMOTE THE DIFFERENTIATION OF B CELLS TO PLASMA CELLS TO PRODUCE MORE AUTOANTIBODIES. METABOLISM-REGULATED CHECKPOINTS AT DIFFERENT STAGES OF THEIR DEVELOPMENT ENSURE THE THAT SELF-REACTIVE B CELLS CLONES AND NEEDLESS PRODUCTION OF INTERLEUKIN (IL-)17 ARE LIMITED. THE METABOLIC REGULATION OF THE TWO CELL TYPES HAS SOME SIMILARITIES, E.G. THE UTILITY OF HYPOXIA INDUCED FACTOR (HIF)1ALPHA DURING LOW OXYGEN TENSION, TO PREVENT AUTOIMMUNITY AND REGULATE INFLAMMATION. THERE ARE ALSO CLEAR DIFFERENCES, AS TH17 CELLS ONLY ARE VULNERABLE TO THE LACK OF CERTAIN AMINO ACIDS. B CELLS, UNLIKE TH17 CELLS, ARE ALSO DEPENDENT OF MECHANISTIC TARGET OF RAPAMYCIN 2 (MTORC2) TO FUNCTION. SIGNIFICANT KNOWLEDGE HAS RECENTLY BEEN GAINED, PARTICULARLY ON TH17 CELLS, ON HOW METABOLISM REGULATES THESE CELLS THROUGH INFLUENCING THEIR EPIGENOME. METABOLIC DYSREGULATION OF TH17 CELLS AND B CELLS CAN LEAD TO CHRONIC INFLAMMATION. DISEASE ASSOCIATED ALTERATIONS IN THE GENOME CAN, IN ADDITION, CAUSE DYSREGULATION TO METABOLISM AND, THEREBY, RESULT IN EPIGENETIC ALTERATIONS IN THESE CELLS. RECENT STUDIES HIGHLIGHT HOW PATHOLOGY CAN RESULT FROM THE COOPERATION BETWEEN THE TWO CELL TYPES BUT ONLY FEW HAVE SO FAR ADDRESSED THE KEY METABOLIC ALTERATIONS IN SUCH SETTINGS. KNOWLEDGE OF THE IMPACT OF METABOLIC DYSFUNCTION ON CHRONIC INFLAMMATION AND PATHOLOGY CAN REVEAL NOVEL THERAPEUTIC TARGETS TO TREAT SUCH DISEASES. 2022 12 295 40 AGING INDUCES B CELL DEFECTS AND DECREASED ANTIBODY RESPONSES TO INFLUENZA INFECTION AND VACCINATION. BACKGROUND: AGING IS CHARACTERIZED BY A PROGRESSIVE DECLINE IN THE CAPACITY OF THE IMMUNE SYSTEM TO FIGHT INFLUENZA VIRUS INFECTION AND TO RESPOND TO VACCINATION. AMONG THE SEVERAL FACTORS INVOLVED, IN ADDITION TO INCREASED FRAILTY AND HIGH-RISK CONDITIONS, THE AGE-ASSOCIATED DECREASE IN CELLULAR AND HUMORAL IMMUNE RESPONSES PLAYS A RELEVANT ROLE. THIS IS IN LARGE PART DUE TO INFLAMMAGING, THE CHRONIC LOW-GRADE INFLAMMATORY STATUS OF THE ELDERLY, ASSOCIATED WITH INTRINSIC INFLAMMATION OF THE IMMUNE CELLS AND DECREASED IMMUNE FUNCTION. RESULTS: AGING IS USUALLY ASSOCIATED WITH REDUCED INFLUENZA VIRUS-SPECIFIC AND INFLUENZA VACCINE-SPECIFIC ANTIBODY RESPONSES BUT SOME ELDERLY INDIVIDUALS WITH HIGHER PRE-EXPOSURE ANTIBODY TITERS, DUE TO A PREVIOUS INFECTION OR VACCINATION, HAVE LESS PROBABILITY TO GET INFECTED. EXAMPLES OF THIS EXCEPTION ARE THE ELDERLY INDIVIDUALS INFECTED DURING THE 2009 PANDEMIC SEASON WHO MADE ANTIBODIES WITH BROADER EPITOPE RECOGNITION AND HIGHER AVIDITY THAN THOSE MADE BY YOUNGER INDIVIDUALS. SEVERAL STUDIES HAVE ALLOWED THE IDENTIFICATION OF B CELL INTRINSIC DEFECTS ACCOUNTING FOR SUB-OPTIMAL ANTIBODY RESPONSES OF ELDERLY INDIVIDUALS. THESE DEFECTS INCLUDE 1) REDUCED CLASS SWITCH RECOMBINATION, RESPONSIBLE FOR THE GENERATION OF A SECONDARY RESPONSE OF CLASS SWITCHED ANTIBODIES, 2) REDUCED DE NOVO SOMATIC HYPERMUTATION OF THE ANTIBODY VARIABLE REGION, 3) REDUCED BINDING AND NEUTRALIZATION CAPACITY, AS WELL AS BINDING SPECIFICITY, OF THE SECRETED ANTIBODIES, 4) INCREASED EPIGENETIC MODIFICATIONS THAT ARE ASSOCIATED WITH LOWER ANTIBODY RESPONSES, 5) INCREASED FREQUENCIES OF INFLAMMATORY B CELL SUBSETS, AND 6) SHORTER TELOMERES. CONCLUSIONS: ALTHOUGH INFLUENZA VACCINATION REPRESENTS THE MOST EFFECTIVE WAY TO PREVENT INFLUENZA INFECTION, VACCINES WITH GREATER IMMUNOGENICITY ARE NEEDED TO IMPROVE THE RESPONSE OF ELDERLY INDIVIDUALS. RECENT ADVANCES IN TECHNOLOGY HAVE MADE POSSIBLE A BROAD APPROACH TO BETTER UNDERSTAND THE AGE-ASSOCIATED CHANGES IN IMMUNE CELLS, NEEDED TO DESIGN TAILORED VACCINES AND EFFECTIVE THERAPEUTIC STRATEGIES THAT WILL BE ABLE TO IMPROVE THE IMMUNE RESPONSE OF VULNERABLE INDIVIDUALS. 2020 13 6809 24 [EPIGENETICS IN INFLAMMATORY SYSTEMIC DISEASES]. IN ADDITION TO ANALYSIS OF THE GENETIC CODE, IN RECENT YEARS MORE AND MORE STUDIES HAVE CONCENTRATED ON CHANGES IN THE EPIGENETIC CODE. EPIGENETIC MECHANISMS DETERMINE WHICH GENES IN A CELL ARE TRANSCRIBED AND THUS FORM THE PHENOTYPE OF A CELL. THE EPIGENETIC CODE CAN BE CHANGED BY ENVIRONMENTAL INFLUENCES, WHICH ALLOWS CELLS TO ADAPT TO LONGSTANDING CHANGES IN THE ENVIRONMENT. THEREFORE, IT IS FEASIBLE TO ASSUME THAT EPIGENETIC CHANGES ARE THE MOLECULAR BASIS FOR LONG-TERM EFFECTS OF THE ENVIRONMENT ON DISEASE DEVELOPMENT. IN PARTICULAR IN TUMORS AND CHRONIC INFLAMMATORY DISEASES EPIGENETIC CHANGES WERE FOUND TO CORRELATE WITH DISEASE SEVERITY AND PROGRESSION. KNOWLEDGE ABOUT THESE EPIGENETIC CHANGES MIGHT HELP THAT EPIGENETIC MODIFICATIONS CAN BE USED IN THE FUTURE AS BIOMARKERS, PROGNOSTIC FACTORS AND THERAPEUTIC TARGETS. 2014 14 3547 48 IMMUNOMODULATORY ROLE OF NUTRIENTS: HOW CAN PULMONARY DYSFUNCTIONS IMPROVE? NUTRITION IS AN IMPORTANT TOOL THAT CAN BE USED TO MODULATE THE IMMUNE RESPONSE DURING INFECTIOUS DISEASES. IN ADDITION, THROUGH DIET, IMPORTANT SUBSTRATES ARE ACQUIRED FOR THE BIOSYNTHESIS OF REGULATORY MOLECULES IN THE IMMUNE RESPONSE, INFLUENCING THE PROGRESSION AND TREATMENT OF CHRONIC LUNG DISEASES, SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN THIS WAY, NUTRITION CAN PROMOTE LUNG HEALTH STATUS. A RANGE OF NUTRIENTS, SUCH AS VITAMINS (A, C, D, AND E), MINERALS (ZINC, SELENIUM, IRON, AND MAGNESIUM), FLAVONOIDS AND FATTY ACIDS, PLAY IMPORTANT ROLES IN REDUCING THE RISK OF PULMONARY CHRONIC DISEASES AND VIRAL INFECTIONS. THROUGH THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY EFFECTS, NUTRIENTS ARE ASSOCIATED WITH BETTER LUNG FUNCTION AND A LOWER RISK OF COMPLICATIONS SINCE THEY CAN DECREASE THE HARMFUL EFFECTS FROM THE IMMUNE SYSTEM DURING THE INFLAMMATORY RESPONSE. IN ADDITION, BIOACTIVE COMPOUNDS CAN EVEN CONTRIBUTE TO EPIGENETIC CHANGES, INCLUDING HISTONE DEACETYLASE (HDAC) MODIFICATIONS THAT INHIBIT THE TRANSCRIPTION OF PROINFLAMMATORY CYTOKINES, WHICH CAN CONTRIBUTE TO THE MAINTENANCE OF HOMEOSTASIS IN THE CONTEXT OF INFECTIONS AND CHRONIC INFLAMMATORY DISEASES. THESE NUTRIENTS ALSO PLAY AN IMPORTANT ROLE IN ACTIVATING IMMUNE RESPONSES AGAINST PATHOGENS, WHICH CAN HELP THE IMMUNE SYSTEM DURING INFECTIONS. HERE, WE PROVIDE AN UPDATED OVERVIEW OF THE ROLES PLAYED BY DIETARY FACTORS AND HOW THEY CAN AFFECT RESPIRATORY HEALTH. THEREFORE, WE WILL SHOW THE ANTI-INFLAMMATORY ROLE OF FLAVONOIDS, FATTY ACIDS, VITAMINS AND MICROBIOTA, IMPORTANT FOR THE CONTROL OF CHRONIC INFLAMMATORY DISEASES AND ALLERGIES, IN ADDITION TO THE ANTIVIRAL ROLE OF VITAMINS, FLAVONOIDS, AND MINERALS DURING PULMONARY VIRAL INFECTIONS, ADDRESSING THE MECHANISMS INVOLVED IN EACH FUNCTION. THESE MECHANISMS ARE INTERESTING IN THE DISCUSSION OF PERSPECTIVES ASSOCIATED WITH SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION AND ITS PULMONARY COMPLICATIONS SINCE PATIENTS WITH SEVERE DISEASE HAVE VITAMINS DEFICIENCY, ESPECIALLY VITAMIN D. IN ADDITION, RESEARCHES WITH THE USE OF FLAVONOIDS HAVE BEEN SHOWN TO DECREASE VIRAL REPLICATION IN VITRO. THIS WAY, A FULL UNDERSTANDING OF DIETARY INFLUENCES CAN IMPROVE THE LUNG HEALTH OF PATIENTS. 2021 15 6135 30 THE EPIGENETICS OF INFLAMMAGING: THE CONTRIBUTION OF AGE-RELATED HETEROCHROMATIN LOSS AND LOCUS-SPECIFIC REMODELLING AND THE MODULATION BY ENVIRONMENTAL STIMULI. A GROWING AMOUNT OF EVIDENCES INDICATES THAT INFLAMMAGING - THE CHRONIC, LOW GRADE INFLAMMATION STATE CHARACTERISTIC OF THE ELDERLY - IS THE RESULT OF GENETIC AS WELL AS ENVIRONMENTAL OR STOCHASTIC FACTORS. SOME OF THESE, SUCH AS THE ACCUMULATION OF SENESCENT CELLS THAT ARE PERSISTENT DURING AGING OR ACCOMPANY ITS PROGRESSION, SEEM TO BE SUFFICIENT TO INITIATE THE AGING PROCESS AND TO FUEL IT. OTHERS, LIKE EXPOSURE TO ENVIRONMENTAL COMPOUNDS OR INFECTIONS, ARE TEMPORARY AND RESOLVE WITHIN A (RELATIVELY) SHORT TIME. IN BOTH CASES, HOWEVER, A CELLULAR MEMORY OF THE EVENT CAN BE ESTABLISHED BY MEANS OF EPIGENETIC MODULATION OF THE GENOME. IN THIS REVIEW WE WILL SPECIFICALLY DISCUSS THE RELATIONSHIP BETWEEN EPIGENETICS AND INFLAMMAGING. IN PARTICULAR, WE WILL SHOW HOW AGE-ASSOCIATED EPIGENETIC MODIFICATIONS CONCERNED WITH HETEROCHROMATIN LOSS AND GENE-SPECIFIC REMODELLING, CAN PROMOTE INFLAMMAGING. FURTHERMORE, WE WILL RECALL HOW THE EXPOSURE TO SPECIFIC NUTRITIONAL, ENVIRONMENTAL AND MICROBIAL STIMULI CAN AFFECT THE RATE OF INFLAMMAGING THROUGH EPIGENETIC MECHANISMS, TOUCHING ALSO ON THE RECENT INSIGHT GIVEN BY THE CONCEPT OF TRAINED IMMUNITY. 2018 16 6344 28 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 17 3676 32 INFLAMMATION AND NEUTROPHIL IMMUNOSENESCENCE IN HEALTH AND DISEASE: TARGETED TREATMENTS TO IMPROVE CLINICAL OUTCOMES IN THE ELDERLY. DESPITE INCREASING LONGEVITY, MANY OLD PEOPLE ARE NOT IN GOOD HEALTH. THERE HAS BEEN AN INCREASE IN THE PREVALENCE OF AGE-ASSOCIATED MULTI-MORBIDITY (TWO OR MORE CHRONIC CONDITIONS IN THE SAME PERSON). ALSO, SEVERE INFECTIONS, SUCH AS PNEUMONIA, REMAIN SIGNIFICANT CAUSES OF MORTALITY AND MORBIDITY IN THIS AGING GROUP. MANY CHRONIC HEALTH CONDITIONS SHARE RISK FACTORS SUCH AS INCREASING AGE, SMOKING, A SEDENTARY LIFE STYLE AND BEING PART OF A LOWER SOCIOECONOMIC GROUP. HOWEVER, DESPITE THIS, MULTI-MORBIDITIES OFTEN CO-OCCUR MORE COMMONLY THAN WOULD BE PREDICTED. THIS HAS LED TO THE HYPOTHESIS THAT THEY SHARE COMMON UNDERLYING MECHANISMS. THIS IS AN IMPORTANT CONCEPT, FOR IF IT WERE TRUE, TREATMENTS COULD BE DEVISED WHICH TARGET THESE COMMON PATHWAYS AND IMPROVE A NUMBER OF AGE-ASSOCIATED HEALTH CONDITIONS. MANY CHRONIC ILLNESSES ASSOCIATED WITH MULTI-MORBIDITY AND SEVERE INFECTIONS ARE CHARACTERIZED BY AN ABNORMAL AND SUSTAINED INFLAMMATORY RESPONSE, WITH NEUTROPHILS BEING KEY EFFECTOR CELLS IN THE PATHOLOGICAL PROCESS. STUDIES HAVE DESCRIBED ABERRANT NEUTROPHIL FUNCTIONS ACROSS THESE CONDITIONS, AND SOME HAVE HIGHLIGHTED POTENTIAL MECHANISMS FOR ALTERED CELL BEHAVIOURS WHICH APPEAR SHARED ACROSS DISEASE STATES. IT HAS BEEN SUGGESTED THAT ALTERED FUNCTIONS MAY REPRESENT NEUTROPHIL "SENESCENCE". THIS REVIEW CONSIDERS HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE CELL AGES, AND HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE HOST AGES IN HEALTH AND DISEASE AND DISCUSSES WHETHER NEUTROPHIL FUNCTIONS COULD BE TARGETED TO IMPROVE HEALTH OUTCOMES IN OLDER ADULTS. 2018 18 5765 29 SOURCE OF CHRONIC INFLAMMATION IN AGING. AGING IS A COMPLEX PROCESS THAT RESULTS FROM A COMBINATION OF ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS. A CHRONIC PRO-INFLAMMATORY STATUS IS A PERVASIVE FEATURE OF AGING. THIS CHRONIC LOW-GRADE INFLAMMATION OCCURRING IN THE ABSENCE OF OVERT INFECTION HAS BEEN DEFINED AS "INFLAMMAGING" AND REPRESENTS A SIGNIFICANT RISK FACTOR FOR MORBIDITY AND MORTALITY IN THE ELDERLY. THE LOW-GRADE INFLAMMATION PERSISTS EVEN AFTER REVERSING PRO-INFLAMMATORY STIMULI SUCH AS LDL CHOLESTEROL AND THE RENIN-ANGIOTENSIN SYSTEM (RAS). RECENTLY, SEVERAL POSSIBLE SOURCES OF CHRONIC LOW-GRADE INFLAMMATION OBSERVED DURING AGING AND AGE-RELATED DISEASES HAVE BEEN PROPOSED. CELL SENESCENCE AND DYSREGULATION OF INNATE IMMUNITY IS ONE SUCH MECHANISM BY WHICH PERSISTENT PROLONGED INFLAMMATION OCCURS EVEN AFTER THE INITIAL STIMULUS HAS BEEN REMOVED. ADDITIONALLY, THE COAGULATION FACTOR THAT ACTIVATES INFLAMMATORY SIGNALING BEYOND ITS ROLE IN THE COAGULATION SYSTEM HAS BEEN IDENTIFIED. THIS SIGNAL COULD BE A NEW SOURCE OF CHRONIC INFLAMMATION AND CELL SENESCENCE. HERE, WE SUMMARIZED THE FACTORS AND CELLULAR PATHWAYS/PROCESSES THAT ARE KNOWN TO REGULATE LOW-GRADE PERSISTENT INFLAMMATION IN AGING AND AGE-RELATED DISEASE. 2018 19 4273 28 MICROBIOTA AND EPIGENETICS: HEALTH IMPACT. EPIGENETIC CHANGES ASSOCIATED WITH DISEASE DEVELOPMENT AND PROGRESSIONS ARE OF INCREASING IMPORTANCE BECAUSE OF THEIR POTENTIAL DIAGNOSTIC AND THERAPEUTIC APPLICATIONS. SEVERAL EPIGENETIC CHANGES ASSOCIATED WITH CHRONIC METABOLIC DISORDERS HAVE BEEN STUDIED IN VARIOUS DISEASES. EPIGENETIC CHANGES ARE MOSTLY MODULATED BY ENVIRONMENTAL FACTORS, INCLUDING THE HUMAN MICROBIOTA LIVING IN DIFFERENT PARTS OF OUR BODIES. THE MICROBIAL STRUCTURAL COMPONENTS AND THE MICROBIALLY DERIVED METABOLITES DIRECTLY INTERACT WITH HOST CELLS, THEREBY MAINTAINING HOMEOSTASIS. MICROBIOME DYSBIOSIS, ON THE OTHER HAND, IS KNOWN TO PRODUCE ELEVATED LEVELS OF DISEASE-LINKED METABOLITES, WHICH MAY DIRECTLY AFFECT A HOST METABOLIC PATHWAY OR INDUCE EPIGENETIC CHANGES THAT CAN LEAD TO DISEASE DEVELOPMENT. DESPITE THEIR IMPORTANT ROLE IN HOST PHYSIOLOGY AND SIGNAL TRANSDUCTION, THERE HAS BEEN LITTLE RESEARCH INTO THE MECHANICS AND PATHWAYS ASSOCIATED WITH EPIGENETIC MODIFICATIONS. THIS CHAPTER FOCUSES ON THE RELATIONSHIP BETWEEN MICROBES AND THEIR EPIGENETIC EFFECTS IN DISEASED PATHOLOGY, AS WELL AS ON THE REGULATION AND METABOLISM OF THE DIETARY OPTIONS AVAILABLE TO THE MICROBES. FURTHERMORE, THIS CHAPTER ALSO PROVIDES A PROSPECTIVE LINK BETWEEN THESE TWO IMPORTANT PHENOMENA, TERMED "MICROBIOME AND EPIGENETICS." 2023 20 6791 31 [DOES THE NUMBER OF PATIENTS WITH AUTOIMMUNE DISORDERS AND THE FREQUENCY OF AUTOIMMUNE DISEASES INCREASE?]. AUTOIMMUNE DISEASES GENERALLY BELONG TO THE RARE DISEASES, HOWEVER, SOME OF THEM ARE FREQUENT IN THE POPULATION. IN THE PRESENT WORK THE AUTHORS ANALYSE WHETHER CAN ANY INCREASE BE OBSERVED IN THE NUMBER OF PATIENTS SUFFERING FROM AUTOIMMUNE DISEASES AND WHETHER DO THE FREQUENCY OF CERTAIN AUTOIMMUNE DISORDERS INCREASE. DUE MAINLY TO EPIGENETIC FACTORS THE INCIDENCE OF AUTOIMMUNE DISEASES ARE INCREASING, THEREFORE THERE ARE MORE PATIENTS RECOGNISED WITH PARTICULAR DISORDERS. ON THE OTHER HAND THE INCIDENCE IS INCREASED BY IMPROVING DIAGNOSTIC POSSIBILITIES, BY THE USE OF MORE SPECIFIC AND SENSITIVE CLASSIFICATION CRITERIA AND MORE SOPHISTICATED LABORATORY TESTS, RESULTED IN THE RECOGNITION OF MILDER AND ATYPICAL DISEASE VARIANTS AS WELL. THE PREVALENCE IS ALSO INCREASING IN CONSEQUENCE OF NOVEL IMMUNE SUPPRESSIVE THERAPEUTIC POSSIBILITIES AND THE CONSEQUENT IMPROVEMENT OF SURVIVAL IN THE MOST OF THESE DISEASES. BESIDES, MORE AND MORE DISEASES HAVE BEEN REVEALED TO HAVE AUTOIMMUNE BACKGROUND, AND LOT OF NEW AUTOIMMUNE SYNDROMES, DISEASES HAVE BEEN CHARACTERISED RECENTLY. THIS INCREASES THE NUMBER OF THE KNOWN AUTOIMMUNE RHEUMATIC DISORDERS WITH A CONSEQUENT INCREASE IN THE NUMBER OF AUTOIMMUNE PATIENTS. ASSIGNED TO THE INCREASING NUMBER OF VARIABLE CHRONIC AUTOIMMUNE DISORDERS, AND THE INCREASING NUMBER OF DISABLED PATIENTS WITH SUCH DISEASES INCREASING MEDICAL AND SOCIAL ATTENTION HAS TO BE FOCUSED ON. 2007