CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus DOI Creative Commons

Mercedes Zubiaur,

Laura C. Terrón‐Camero,

Fernando Gordillo-González

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 10, 2025

This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with autoimmune response in Cd38 -/- mice compared wild-type (WT) within bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) spleen (SPC) at two four weeks following adoptive cell transfer. also analyzed from healthy, untreated mice. These analyses revealed a sustained upregulation of transcriptional profile purinergic receptors ectonucleotidases cGVHD WT PECs, which displayed coordinated expression several type I interferon-stimulated genes (ISGs) key molecules involved cyclic GMP-AMP synthase-stimulator interferon (cGAS-STING) signaling pathway, hallmarks pathology. A second receptor profile, included P2rx7 P2rx4 , showed gene components NLRP3 inflammasome its potential activators. processes were transcriptionally less active PECs than PECs. have shown evidence distinct enrichment that define such as Ca 2+ ion homeostasis, division, phagosome, autophagy, senescence, cytokine/cytokine interactions, Th17 Th1/Th2 differentiation versus samples, reflected milder inflammatory elicited relative counterparts allogeneic challenge. Last, we an intense metabolic reprogramming toward oxidative phosphorylation SPC mice, may reflect increased cellular demand for oxygen consumption, contrast short-lived effect level. Overall, these findings support pro-inflammatory immunomodulatory role CD38 during development cGVHD-lupus disease.

Язык: Английский

Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism DOI Creative Commons
Nils Mülling, Felix M. Behr, Graham A. Heieis

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(17)

Опубликована: Июль 2, 2024

Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying disability cytotoxic T cells to provide sufficient protection against CMV immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling CMV-specific CD8+ patients immunocompromised show development dysregulation at transcriptional, protein, functional level KTRs with noncontrolled infection. These dysregulations comprise impaired glycolysis increased mitochondrial stress, which associated an intensified expression nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity CD38 reinvigorated metabolism improved cytokine production cells. findings were corroborated a mouse model infection under conditions immunosuppression. Thus, dysregulated states could be targeted by inhibiting reverse hyporesponsiveness individuals fail control chronic viral

Язык: Английский

Процитировано

3
Lymphocytes Change Their Phenotype and Function in Systemic Lupus Erythematosus and Lupus Nephritis DOI Open Access
Eleni Moysidou, Michalis Christodoulou, Γεώργιος Λιούλιος

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(20), С. 10905 - 10905

Опубликована: Окт. 10, 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, characterized by considerable changes in peripheral lymphocyte structure and function, that plays critical role commencing reviving the inflammatory immune signaling pathways. In healthy individuals, B lymphocytes have major guiding directing defense mechanisms against pathogens. Certain phenotype, including alterations surface endosomal receptors, occur presence of SLE lead to dysregulation subpopulations. Functional are loss self-tolerance, intra- extrafollicular activation, increased cytokine autoantibody production. T seem supporting, rather than leading, disease pathogenesis. Substantial aberrations subsets evident, include reduction cytotoxic, regulatory, advanced differentiated subtypes, together with an increase activated autoreactive forms abnormalities follicular cells. Up-regulated subpopulations, such as central effector memory cells, produce pre-inflammatory cytokines, activate lymphocytes, stimulate cell This review explores pivotal roles pathogenesis Lupus Nephritis, emphasizing multifaceted interactions their phenotypic functional dysregulations.

Язык: Английский

Процитировано

3
Unraveling the immunomodulatory impact of hydroxychloroquine on peripheral T cells using single-cell RNA sequencing DOI Creative Commons

H. F. Long,

Luís Manzano, Amr H. Sawalha

и другие.

Journal of Autoimmunity, Год журнала: 2024, Номер 149, С. 103324 - 103324

Опубликована: Окт. 13, 2024

Язык: Английский

Процитировано

3
Lower circulating mitochondrial DNA and increased mitokines suggest significant mitochondrial dysfunction in systemic lupus erythematosus with renal involvement DOI Creative Commons
Matthieu Halfon, Ashfaque A. Memon,

Anna Hedelius

и другие.

Lupus Science & Medicine, Год журнала: 2025, Номер 12(1), С. e001368 - e001368

Опубликована: Фев. 1, 2025

Background SLE is associated with significant morbidity, especially in the case of renal involvement. Mitochondrial dysfunction plays a role and may be assessed by measuring mitochondrial DNA (mtDNA) cytokines reflecting stress (mitokines). Circulating mtDNA promising biomarker appears to reduced severe SLE. However, circulating challenging reported methods are heterogenous. Our study aimed at evaluating whole blood nuclear (nucDNA) ratio using droplet-digital PCR mitokines, growth differentiation factor 15 (GDF-15) fibroblast 21 without Methods Cross-sectional involving 195 patients age-matched healthy volunteers (HV) as control. Biomarkers were compared involvement (defined estimated glomerular filtration rate <60 mL/min or proteinuria >0.5 g/day) those active inactive Results Compared HV, displayed lower mtDNA/nucDNA ratios, Accordingly, mitokines increased We found no correlation between global disease activity. Mitokine levels, on other hand, correlated activity, particular GDF-15 even after adjusting for Conclusion findings suggest that ratio, surrogate marker dysfunction, reflects damage, while also reflect activity Further studies needed assess clinical value these markers predictors lupus nephritis.

Язык: Английский

Процитировано

0
CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus DOI Creative Commons

Mercedes Zubiaur,

Laura C. Terrón‐Camero,

Fernando Gordillo-González

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 10, 2025

This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with autoimmune response in Cd38 -/- mice compared wild-type (WT) within bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) spleen (SPC) at two four weeks following adoptive cell transfer. also analyzed from healthy, untreated mice. These analyses revealed a sustained upregulation of transcriptional profile purinergic receptors ectonucleotidases cGVHD WT PECs, which displayed coordinated expression several type I interferon-stimulated genes (ISGs) key molecules involved cyclic GMP-AMP synthase-stimulator interferon (cGAS-STING) signaling pathway, hallmarks pathology. A second receptor profile, included P2rx7 P2rx4 , showed gene components NLRP3 inflammasome its potential activators. processes were transcriptionally less active PECs than PECs. have shown evidence distinct enrichment that define such as Ca 2+ ion homeostasis, division, phagosome, autophagy, senescence, cytokine/cytokine interactions, Th17 Th1/Th2 differentiation versus samples, reflected milder inflammatory elicited relative counterparts allogeneic challenge. Last, we an intense metabolic reprogramming toward oxidative phosphorylation SPC mice, may reflect increased cellular demand for oxygen consumption, contrast short-lived effect level. Overall, these findings support pro-inflammatory immunomodulatory role CD38 during development cGVHD-lupus disease.

Язык: Английский

Процитировано

0