IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation DOI
Peyton Conrey, Lidiya Denu, Kaitlin C. O’Boyle

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(83)

Published: May 26, 2023

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on larger scale, whether systemic anti-commensal responses are redundant or unique features. To address this gap knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry metagenomic sequencing (mFLOW-Seq) comprehensively define which microbes induce antibodies. We coupled high-dimensional immune profiling study cohort pediatric SIgAD household control siblings. found that antibody networks cooperate maintain homeostasis by targeting common subset commensal microbes. In IgA-deficiency, find increased translocation specific bacterial taxa associated elevated levels IgG fecal microbiota. Associated features dysregulation IgA-deficient mice humans included inflammatory cytokines, enhanced follicular CD4 T helper cell frequency activation, altered CD8 activation state. Although is clinically defined absence serum IgA, symptomatology were concentrated participants who also deficient. These findings reveal leads aberrant exposures microbes, increase likelihood humoral cellular symptomatic disease deficiency.

Language: Английский

The total mass, number, and distribution of immune cells in the human body DOI Creative Commons
Ron Sender, Yarden Weiss,

Yoav Navon

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(44)

Published: Oct. 23, 2023

The immune system is a complex network of cells with critical functions in health and disease. However, comprehensive census the comprising lacking. Here, we estimated abundance primary cell types throughout all tissues human body. We conducted literature survey integrated data from multiplexed imaging methylome-based deconvolution. also considered cellular mass to determine distribution terms both number total mass. Our results indicate that reference 73 kg man consists 1.8 × 10 12 (95% CI 1.5–2.3 ), weighing 1.2 0.8–1.9). Lymphocytes constitute 40% 15% are mainly located lymph nodes spleen. Neutrophils account for similar proportions cells, most neutrophils residing bone marrow. Macrophages, present tissues, 10% but contribute nearly 50% due their large size. quantification within body presented here can serve understand function better facilitate quantitative modeling this vital system.

Language: Английский

Citations

118

Alterations of host-gut microbiome interactions in multiple sclerosis DOI Creative Commons
Claudia Cantoni, Qingqi Lin, Yair Dorsett

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 76, P. 103798 - 103798

Published: Jan. 27, 2022

Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between host system, metabolism diet have not been studied over time this disorder.We performed six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting patients 25 age, sex, race matched healthy control individuals. Gut composition function were characterized using 16S metagenomic shotgun sequencing. Flow cytometry was used to characterize blood cell populations cytokine profiles. Circulating metabolites profiled by untargeted UPLC-MS. A four-day food diary recorded capture habitual dietary pattern participants.Together with changes cells, analysis identified number microbiota decreased compared controls, positively or negatively correlated degree disability patients. demonstrated perturbations their metabolome, such as linoleate pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol methionine. Global correlations disrupted immune-microbiome relationship positive metabolome-microbiome correlation MS. Specific feature association potential network linking meat servings microbe B. thetaiotaomicron, increased Th17 greater abundance meat-associated metabolites. The metabolome profiles remained stable six months individuals.Our multi-system alterations microbiota, at global individual level. Multi-OMICS data integration deciphered important biological that links intakes metabolite, polysaccharides digesting bacteria, circulating proinflammatory marker.This work supported Washington University St. Louis Institute Clinical Translational Sciences, funded, part, Grant Number # UL1 TR000448 from National Institutes Health, Center for Advancing Sciences Award (Zhou Y, Piccio, L, Lovett-Racke Tarr PI); R01 NS10263304 Piccio L); Leon Harriet Felman Fund Human Research (Piccio L Cross AH). Cantoni C. Society Career Transition Fellowship (TA-180531003) donations Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. Italian Sclerosis research fellowship (FISM 2018/B/1) Post-Doctoral (FG-190734474). Anne Manny & Rosalyn Rosenthal-Dr. John Trotter Chair Neuroimmunology Barnes-Jewish Hospital Foundation. content is solely responsibility authors does necessarily represent official views Health.

Language: Английский

Citations

99

Improving the study of brain-behavior relationships by revisiting basic assumptions DOI Creative Commons
Christiana Westlin, Jordan E. Theriault, Yuta Katsumi

et al.

Trends in Cognitive Sciences, Journal Year: 2023, Volume and Issue: 27(3), P. 246 - 257

Published: Feb. 2, 2023

Neuroimaging research has been at the forefront of concerns regarding failure experimental findings to replicate. In study brain-behavior relationships, past failures find replicable and robust effects have attributed methodological shortcomings. Methodological rigor is important, but there are other overlooked possibilities: most published studies share three foundational assumptions, often implicitly, that may be faulty. this paper, we consider empirical evidence from human brain imaging non-human animals calls each assumption into question. We then opportunities for a science relationships await if scientists ground their efforts in revised assumptions supported by current evidence.

Language: Английский

Citations

95

Vitamin D as a Shield against Aging DOI Open Access
Cristina Fantini, Clarissa Corinaldesi, Andrea Lenzi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4546 - 4546

Published: Feb. 25, 2023

Aging can be seen as a physiological progression of biomolecular damage and the accumulation defective cellular components, which trigger amplify process, toward whole-body function weakening. Senescence initiates at level consists in an inability to maintain homeostasis, characterized by overexpression/aberrant expression inflammatory/immune/stress responses. is associated with significant modifications immune system cells, decline immunosurveillance, which, turn, leads chronic elevation inflammation/oxidative stress, increasing risk (co)morbidities. Albeit aging natural unavoidable it regulated some factors, like lifestyle diet. Nutrition, indeed, tackles mechanisms underlying molecular/cellular aging. Many micronutrients, i.e., vitamins elements, impact cell function. This review focuses on role exerted vitamin D geroprotection, based its ability shape cellular/intracellular processes drive response protection against infections age-related diseases. To this aim, main paths immunosenescence inflammaging are identified biotargets D. Topics such heart skeletal muscle function/dysfunction, depending status, addressed, comments hypovitaminosis correction food supplementation. research has progressed, still limitations exist translating knowledge into clinical practice, making necessary focus attention aging, especially considering growing number older individuals.

Language: Английский

Citations

56

IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation DOI
Peyton Conrey, Lidiya Denu, Kaitlin C. O’Boyle

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(83)

Published: May 26, 2023

The ability of most patients with selective immunoglobulin A (IgA) deficiency (SIgAD) to remain apparently healthy has been a persistent clinical conundrum. Compensatory mechanisms, including IgM, have proposed, yet it remains unclear how secretory IgA and IgM work together in the mucosal system and, on larger scale, whether systemic anti-commensal responses are redundant or unique features. To address this gap knowledge, we developed an integrated host-commensal approach combining microbial flow cytometry metagenomic sequencing (mFLOW-Seq) comprehensively define which microbes induce antibodies. We coupled high-dimensional immune profiling study cohort pediatric SIgAD household control siblings. found that antibody networks cooperate maintain homeostasis by targeting common subset commensal microbes. In IgA-deficiency, find increased translocation specific bacterial taxa associated elevated levels IgG fecal microbiota. Associated features dysregulation IgA-deficient mice humans included inflammatory cytokines, enhanced follicular CD4 T helper cell frequency activation, altered CD8 activation state. Although is clinically defined absence serum IgA, symptomatology were concentrated participants who also deficient. These findings reveal leads aberrant exposures microbes, increase likelihood humoral cellular symptomatic disease deficiency.

Language: Английский

Citations

42