Chronic inflammation and the hallmarks of aging

Molecular Metabolism, Год журнала: 2023, Номер 74, С. 101755 - 101755

Опубликована: Июнь 16, 2023

Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, low-grade inflammation during aging, without overt infection, is defined as "inflammaging," which associated with increased morbidity mortality in population. Emerging evidence suggests a bidirectional cyclical relationship between development age-related conditions, such cardiovascular diseases, neurodegeneration, cancer, frailty. How crosstalk other underlies biological mechanisms disease thus particular interest current geroscience research.

Язык: Английский

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Memory B cells

Nature reviews. Immunology, Год журнала: 2023, Номер 24(1), С. 5 - 17

Опубликована: Июль 3, 2023

Язык: Английский

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Age-associated B cells contribute to the pathogenesis of rheumatoid arthritis by inducing activation of fibroblast-like synoviocytes via TNF-α-mediated ERK1/2 and JAK-STAT1 pathways

Annals of the Rheumatic Diseases, Год журнала: 2022, Номер 81(11), С. 1504 - 1514

Опубликована: Июнь 27, 2022

Age-associated B cells (ABCs) are a recently identified cell subset, whose expansion has been increasingly linked to the pathogenesis of autoimmune disorders. This study aimed investigate whether ABCs involved in and underlying mechanisms rheumatoid arthritis (RA).ABCs were assessed collagen-induced (CIA) mice patients with RA using flow cytometry. Transcriptomic features explored RNA-seq. Primary fibroblast-like synoviocytes (FLS) derived from synovial tissue cocultured or ABCs-conditioned medium (ABCsCM). IL-6, MMP-1, MMP-3 MMP-13 levels coculture supernatant detected by ELISA. Signalling pathways related ABCs-induced FLS activation examined western blotting.Increased blood, spleen inflammatory joints CIA observed. Notably, elevated fluid positively correlated disease activity. RNA-seq revealed upregulated chemotaxis-related genes compared those naive memory cells. Coculture ABCsCM led an active phenotype FLS, increased production MMP-13. Mechanistically, ABCsCM-derived TNF-α promoted upregulation interferon-stimulated phosphorylation ERK1/2 STAT1. Furthermore, blockage Janus Kinase (JAK)-STAT1 inhibited induced ABCsCM.Our results suggest that contribute inducing via TNF-α-mediated JAK-STAT1 pathways.

Язык: Английский

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An aging-related immune landscape in the hematopoietic immune system

Immunity & Ageing, Год журнала: 2024, Номер 21(1)

Опубликована: Янв. 2, 2024

Aging is a holistic change that has major impact on the immune system, and immunosenescence contributes to overall progression of aging. The bone marrow most important hematopoietic organ, while spleen, as extramedullary maintains homeostasis human system (HIS) in cooperation with marrow. However, changes HIS during aging have not been described. Here, we describe map spleen young old mice using single-cell sequencing flow cytometry techniques.

Язык: Английский

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Immune aging – A mechanism in autoimmune disease

Seminars in Immunology, Год журнала: 2023, Номер 69, С. 101814 - 101814

Опубликована: Авг. 3, 2023

Язык: Английский

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Sex/gender-related differences in inflammaging

Mechanisms of Ageing and Development, Год журнала: 2023, Номер 211, С. 111792 - 111792

Опубликована: Фев. 17, 2023

Geroscience puts mechanisms of aging as a driver the most common age-related diseases and dysfunctions. Under this perspective, addressing basic will produce better understanding than each disease pathophysiology individually. Worldwide, despite greater functional impairment, life expectancy is higher in women men. Gender differences prevalence multimorbidity lead mandatory to underlying gender-related patterns disability-free expectancy. Extensive literature suggested that inflammaging at crossroad diseases. In review, we highlight main evidence on sex/gender foster inflammaging, i.e. age-dependent triggering innate immunity, modifications adaptive accrual senescent cells, underpinning some biomarkers show sex-related differences. framework "gender medicine perspective", also discuss how can affect sex COVID-19 severe outcomes.

Язык: Английский

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Immune dysregulation

Journal of Allergy and Clinical Immunology, Год журнала: 2023, Номер 151(1), С. 70 - 80

Опубликована: Янв. 1, 2023

The understanding of immune dysregulation in many different diseases continues to grow. There is increasing evidence that altered microbiome and gut barrier dysfunction contribute systemic inflammation patients with primary immunodeficiency rheumatic disease. Recent research provides insight into the process induction maturation pathogenic age-associated B cells highlights role creating tissue inflammation. T follicular regulatory are shown help maintain B-cell tolerance, therapeutic approaches increase or promote may prevent decrease dysregulation. Meanwhile, novel studies systemic-onset juvenile idiopathic arthritis reveal a strong HLA association interstitial lung disease identify key aspects pathogenesis macrophage activation syndrome. Studies hyperinflammatory syndromes, including recently described multisystem inflammatory syndrome children, characterize similarities differences cytokine profiles T-cell activation. This review focuses on recent advances describes potential factors function as biomarkers for targets interventions. Future trials necessary address remaining questions regards pathogenesis, diagnosis, treatment autoimmune, inflammatory, syndromes. Immune can manifest autoimmunity, autoinflammation, allergy, lymphoproliferation. In inborn error immunity (IEI), these often referred noninfectious complications. has been reported all major categories IEI be initial presentation IEI.1Thalhammer J. Kindle G. Nieters A. Rusch S. Seppanen M.R.J. Fischer et al.Initial presenting manifestations 16,486 errors include infections manifestations.J Allergy Clin Immunol. 2021; 148: 1332-1341.e5Abstract Full Text PDF PubMed Scopus (27) Google Scholar, 2Mauracher A.A. Gujer E. Bachmann L.M. Gusewell Pachlopnik Schmid Patterns immunodeficiencies: systematic review.J Immunol Pract. 9: 792-802.e10Abstract (9) 3Resnick E.S. Moshier E.L. Godbold J.H. Cunningham-Rundles C. Morbidity mortality common variable deficiency over 4 decades.Blood. 2012; 119: 1650-1657Crossref (515) 4Ho H.E. Non-infectious complications immunodeficiency: updated clinical spectrum, sequelae, insights pathogenesis.Front 2020; 11: 149Crossref (67) Scholar (CVID), rather than infection cause mortality.3Resnick also seen much more polygenetic immune-mediated (IMIDs). lessons learned from applicable IMIDs, vice versa. will focus selective relevance immunologists (Table I).Table IImportant concepts dysregulationImpaired intestinal increases risk autoimmunity1. CVID, low IgA, switched memory cells, increased CXCL10 levels associated complications.7Abyazi M.L. Bell K.A. Gyimesi Baker T.S. Byun M. Ko H.M. al.Convergence antibody complications.J 2022; 149: 315-326.e9Abstract (0) Scholar,8Ho Seeking relevant immunodeficiency.Front 13857050Crossref Scholar2. serum bacterial DNA zonulin IFN-γ autoimmunity.9Ho Radigan L. Bongers El-Shamy Circulating bioactive immunodeficiency.JCI Insight. Crossref (5) Scholar3. Peripheral blood mononuclear X-linked agammaglobulinemia have defective response mimicked BTK inhibitor.9Ho Scholar4. Intestinal precedes development RA mouse models collagen-induced (CIA).10Tajik N. Frech Schulz O. Schalter F. Lucas Azizov V. al.Targeting epithelial onset arthritis.Nat Commun. 1995Crossref (127) Scholar,11Matei D.E. Menon Alber D.G. Smith A.M. Nedjat-Shokouhi B. Fasano al.Intestinal plays an integral pathology targeted ameliorate disease.Med (N Y). 2: 864-883.e9PubMed Scholar5. Prevention ameliorates CIA.10Tajik ScholarABCs play important autoimmune disease1. marked expansion ABCs CVID HIV, but similar SLE.26Keller Strohmeier Harder I. Unger Payne K.J. Andrieux al.The human T-bethighCD21low cell dependent.Sci 6eabh0891Crossref (25) Induction requires CD4 expression CD40 ligand, IL-21, IFN-γ.3. TH1 stimulate produce IFN-γ–induced chemokines CXCL9 CXCL10.28Nakayama T. Yoshimura Higashioka K. Miyawaki Ota Y. Ayano al.Type 1 helper generate CXCL9/10-producing T-bet+ effector potentially involved rheumatoid arthritis.Cell 360104263Crossref (6) expanded lungs granulomatous patients, synovium patients.26Keller 27Rakhmanov Keller Gutenberger Foerster Hoenig Driessen al.Circulating CD21low resemble homing, innate-like cells.Proc Natl Acad Sci U S 2009; 106: 13451-13456Crossref (242) 28Nakayama 29Friedmann D. Rakhmanov Goldacker Zissel al.Bronchoalveolar lavage fluid reflects TH1-CD21low interaction CVID-related disease.Front 11616832Google 30Phalke Aviszus Rubtsova Rubtsov Barkes Powers al.Age-associated appear diseases.Am J Respir Crit Care Med. 202: 1013-1023Crossref (15) ScholarTreg Tfr mediate peripheral self-tolerance1. second checkpoint humoral tolerance mediated by recognizing self-antigen cells.33Samuels Ng Y.S. Coupillaud Paget Meffre Impaired early arthritis.J Exp 2005; 201: 1659-1667Crossref Scholar,34Chen J.W. Schickel J.N. Tsakiris Sng Arbogast Bouis al.Positive negative selection shape naive repertoire.J Invest. (2) Neuritin, neuropeptide secreted mediates suppression autoantibody production IgE production.40Gonzalez-Figueroa P. Roco J.A. Papa Nunez Villacis Stanley Linterman M.A. al.Follicular neuritin regulate cells.Cell. 184: 1775-1789.e19Abstract (36) ScholarEBV linked EBV factor multiple sclerosis SLE.43Bjornevik Cortese Healy B.C. Kuhle Mina M.J. Leng al.Longitudinal analysis reveals high prevalence Epstein-Barr virus sclerosis.Science. 375: 296-301Crossref (278) 44Robinson W.H. Steinman 264-265Crossref (22) 45He R. Du Wang infection: leading sclerosis.Signal Transduct Target Ther. 7: 239Crossref 46James Kaufman K.M. Farris A.D. Taylor-Albert Lehman T.J. Harley J.B. An young suggests possible etiology lupus erythematosus.J 1997; 100: 3019-3026Crossref 47Laurynenka Ding James A anti-EBNA1 heteroantibodies erythematosus (SLE) supports origin SLE autoantibodies.Front 13830993Crossref 48Jog N.R. McClain M.T. Heinlen L.D. Gross Towner Guthridge J.M. al.Epstein Barr nuclear antigen (EBNA-1) peptides recognized adult patient sera induce neurologic symptoms murine model.J Autoimmun. 106102332Crossref (19) 49Singh Oudit Hajtovic Sarbaugh Salis Adebowale al.Antibodies Epstein protein cross-react dsDNA potential.Mol 132: 41-52Crossref γHV68 (a herpesvirus mimics EBV) expands CIA experimental encephalomyelitis.23Mouat I.C. Goldberg Horwitz M.S. Age-associated diseases.Cell Mol Life Sci. 79: 402Crossref (4) Scholar,50Mouat Morse Z.J. Shanina Brown K.L. Latent gammaherpesvirus exacerbates through modification cells.Elife. 10e67024Crossref (8) Scholar,51Mouat viral infection.PLoS Pathog. 18e1010297Crossref ScholarPediatric syndromes such MAS-SOJIA, LD-SOJIA, MIS-C characterized IFN-γ, IL-18, IL-1β1. Monocytes MAS-SOJIA TRIM8, which ubiquitin ligase upregulates interferon signaling.53Schulert G.S. Pickering A.V. Do Dhakal Fall Schnell al.Monocyte bone marrow transcriptional phenotypes TRIM8 mediator IFN-gamma hyper-responsiveness syndrome.Ann Rheum Dis. 80: 617-625Crossref (11) Preliminary results open-label trial anti–IFN-γ monoclonal show 11 14 experiencing remission 8 weeks.3. IL-1 inhibition possibly because promotes type I production, IL-18 levels.59Quartier Allantaz Cimaz Pillet Messiaen Bardin al.A multicentre, randomised, double-blind, placebo-controlled interleukin-1 receptor antagonist anakinra (ANAJIS trial).Ann 2011; 70: 747-754Crossref (412) Scholar,60Verweyen Holzinger Weinhage Hinze Wittkowski H. Pickkers al.Synergistic signaling TLR IFNalpha/beta facilitates escape endotoxin tolerance.Am 526-539Crossref Proteomic LD-SOJIA differentiated.65Chen Deutsch G.H. Schulert Zheng Jang Trapnell al.Identification distinct programs related proteome analysis.Arthritis Rheumatol. 74: 1271-1283Crossref (3) HLA-DRB1∗1501 strongly LD-SOJIA.65Chen Scholar,69Saper V.E. Ombrello Tremoulet A.H. Montero-Martin Prahalad Canna al.Severe delayed hypersensitivity reactions IL-6 inhibitors link HLA-DRB1∗15 alleles.Ann 81: 406-415Crossref Scholar6. KD MIS-C, IVIG eliminates hyperactive neutrophils express IL-1β.90Zhu Y.P. Shamie Lee J.C. Nowell C.J. Peng W. Angulo al.Immune intravenous immunoglobulin Kawasaki MIS-C.J (12) Scholar7. highest followed SOJIA, then MIS-C.88Rodriguez-Smith J.J. Verweyen Clay G.M. Esteban Y.M. de Loizaga S.R. E.J. al.Inflammatory COVID-19–associated disease, syndrome: cohort study.Lancet 3: e574-e584Abstract Scholar8. spike protein, act superantigen, leaking GI tract decreased larazotide, antagonist.85Yonker Gilboa Ogata A.F. Senussi Lazarovits Boribong B.P. al.Multisystem children driven zonulin-dependent loss mucosal barrier.J (74) Scholar,86Yonker Swank Z. Kenyon Papadakis al.Zonulin antagonist, larazotide (AT1001), adjuvant children: case series.Crit Explor. 10e0641Crossref Open table new tab identical twins discordant same genotype dramatically phenotypes.5Rodriguez-Cortez V.C. Del Pino-Molina Rodriguez-Ubreva Ciudad Gomez-Cabrero Company al.Monozygotic impaired demethylation during naive-to-memory transition.Nat 2015; 6: 7335Crossref Scholar,6Rodriguez-Ubreva Arutyunyan Bonder Clark S.J. la Calle-Fabregat al.Single-cell Atlas shows germinal center-associated epigenetic responses.Nat 13: 1779Crossref implication environmental almost certainly role. articles given us detailed picture linking microbial products (Fig 1). Multi-omics used take fresh look at patients.7Abyazi Soluble CD14, marker monocyte activation, was correlated elevated cytokines, lower especially IgA IgM antibodies binding lipopolysaccharide. Unsupervised machine learning data found top 3 contributors cluster assignment were chemokine induced IFN-γ), (both total isotype LPS specific) isotype-switched cells. These consistent model defects immunity, lead dysfunction, translocation bacteria, both innate adaptive arms system, infiltration and/or autoimmunity. importance other reviewed.8Ho another article, DNA, (XLA) compared healthy controls, appeared activation.9Ho Sequencing indicated commensal source circulating DNA. Zonulin fatty acid two markers small permeability defects, versus health controls. Moreover, significantly higher had IFN-γ. Interestingly, vitro greater complications, suggesting vivo priming. authors point out finding inconsistent earlier studies. this study, not despite using assays. Thus, biomarker activates immunity. part study XLA. While XLA they did sCD14, LBP, zonulin, protein. inhibitor Bruton tyrosine kinase (BTK) blocked DNA–induced normal mutant explain their rate CVID. IMIDs. targeting disruption treat inflammation.10Tajik only (RA) subset pre-RA (anti-CCP positive no synovitis).10Tajik progressed course 12 months baseline. Because controversy about assay,12Fasano measurement conundrum: add confusion does clarity.Gut. 2007-2008Crossref (7) corroborated 2 established assays dysfunction: first, tight junction proteins biopsy samples terminal ileum, second, ratio lactulose absorption mannitol absorption. arthritis, zonulin; lactulose/mannitol absorption, fluorescein isothiocyanate (aka FITC)-dextran. Of note, models, began before synovitis occurred. synthetic peptide, blocks zonula occludin toxin ZOT) zonulin. animal permeability, score, periarticular loss. already being trials.13Hoilat G.J. Altowairqi A.K. Ayas M.F. Alhaddab N.T. Alnujaidi R.A. Alharbi H.A. al.Larazotide acetate celiac disease: meta-analysis randomized controlled trials.Clin Res Hepatol Gastroenterol. 46101782Crossref Other interventions block permeability—such short chain butyrate cannabinoid inhibitors—had effects score. Most intriguingly, track migration (using UV light–activated transgenic tag) demonstrate migrate gastrointestinal (GI) synovial animals arthritis. license target tissues. Recently article confirmed bowel homing (CCR9+α4β7+) well activity (DAS28).11Matei expressing T-bet first demonstrated 2002, B-cell–specific deletion.14Peng S.L. Szabo Glimcher L.H. regulates IgG class switching production.Proc 2002; 99: 5545-5550Crossref (369) That year, between cytopenias reported.15Warnatz Wehr Drager Schmidt Eibel Schlesier al.Expansion CD19hiCD21lo/neg (CVID) cytopenia.Immunobiology. 206: 502-513Crossref studying sex aging Philippa Marrack’s lab observed myeloid CD11c CD11b age female mice.16Rubtsov Meehan R.T. Gillis J.Z. Kappler al.Toll-like 7 (TLR7)-driven accumulation CD11c+ population autoimmunity.Blood. 118: 1305-1315Crossref (399) young, prone mice women RA. termed ABCs, abbreviation still used.17Cancro M.P. cells.Annu Rev 38: 315-340Crossref (105) companion Michael Cancro’s identified aging.18Hao O’Neill Naradikian Scholz J.L. Cancro uniquely responsive stimuli accumulates aged mice.Blood. 1294-1304Crossref (294) Subsequent CD21lowCD11+ autoimmunity chronic infections.19Myles Sanz cells: denominator protective autoreactive responses?.Curr Opin 2019; 57: 40-45Crossref (13) 20Rubtsova Marrack T-bet–dependent roles immunity.J 195: 1933-1937Crossref (120) 21Sanz Wei Jenks S.A. Cashman K.S. Tipton Woodruff M.C. al.Challenges opportunities classification plasma populations.Front 10: 2458Crossref (148) 22Phalke Rivera-Correa Jenkins Flores Castro Giannopoulou Pernis A.B. Molecular mechanisms controlling autoimmunity.Immunol Rev. 307: 79-100Crossref (10) 23Mouat 2018, phenotype (CXCR3+CCR6−) lymph nodes complications.24Unger Seidl van Schouwenburg Bulashevska Frede indicates IFN-gamma–associated immunodeficiency.J 2018; 141: 730-740Abstract Expansion T-bet+CD21low nodes. individual having “largely normal” lacking CD21lowCD11c+ cells.25Yang Avery D.T. Jackson K.J.L. Ogishi Benhsaien al.Human governs generation CD11chighCD21low cells.Sci 7eabq3277Crossref Therefore, directed reducing depletion anti-CD20 anti-CD19 antibodies, mitigate without blocking responses. analyzed great detail.26Keller

Язык: Английский

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Single-cell profiling reveals age-associated immunity in atherosclerosis

Cardiovascular Research, Год журнала: 2023, Номер 119(15), С. 2508 - 2521

Опубликована: Июнь 30, 2023

Aging is a dominant driver of atherosclerosis and induces series immunological alterations, called immunosenescence. Given the demographic shift towards elderly, elucidating unknown impact aging on landscape in highly relevant. While young Western diet-fed Ldlr-deficient (Ldlr-/-) mouse widely used model to study atherosclerosis, it does not reflect gradual plaque progression context an immune system as occurs humans.

Язык: Английский

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From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 24, 2023

The process of aging is accompanied by a dynamic restructuring the immune response, phenomenon known as immunosenescence. This mini-review navigates through complex landscape age-associated changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology Long COVID. Immunosenescence serves an introductory departure point, elucidating alterations in cell profiles functional dynamics, changes T-cell receptor signaling, cytokine network dysregulation, compromised regulatory function. Subsequent scrutiny or “inflammaging,” highlights its roles susceptibilities mediator perturbations observed COVID patients. introduction epigenetic facets further amplifies interconnections. In this compact review, we consider interactions between immunosenescence, autoimmunity. We aim to explore multifaceted relationships that link these processes shed light on underlying mechanisms drive interconnectedness. With focus understanding immunological context aging, seek provide insights into how immunosenescence inflammation contribute emergence progression disorders elderly may serve for disturbances.

Язык: Английский

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Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 27, 2023

Abstract Age-associated B cells (ABC) accumulate with age and in individuals different immunological disorders, including cancer patients treated immune checkpoint blockade those inborn errors of immunity. Here, we investigate whether ABCs from conditions are similar how they impact the longitudinal level COVID-19 vaccine response. Single-cell RNA sequencing indicates that distinct aetiologies have common transcriptional profiles can be categorised according to their expression genes, such as autoimmune regulator ( AIRE ). Furthermore, higher baseline ABC frequency correlates decreased levels antigen-specific memory reduced neutralising capacity against SARS-CoV-2. express high inhibitory FcγRIIB receptor distinctive ability bind complexes, which could contribute diminish responses either directly, or indirectly via enhanced clearance complexed-antigen. Expansion may, therefore, serve a biomarker identifying at risk suboptimal vaccination.

Язык: Английский

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