Leukemic cell-secreted interleukin-9 suppresses cytotoxic T cell-mediated killing in chronic lymphocytic leukemia DOI Open Access
Gioia Boncompagni, Vanessa Tatangelo, Ludovica Lopresti

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 24, 2023

ABSTRACT The tumor microenvironment (TME) plays a central role in the pathogenesis of chronic lymphocytic leukemia (CLL), contributing to disease progression and chemoresistance. Leukemic cells shape TME into pro-survival immunosuppressive niche through contact-dependent contact-independent interactions with cellular components TME. Immune synapse (IS) formation is defective CLL. Here we asked whether soluble factors released by CLL contribute their protection from cytotoxic T cell (CTL)-mediated killing interfering this process. We found that healthy CTLs cultured media conditioned leukemic patients or Eμ-TCL1 mice upregulate exhaustion marker PD-1 become unable form functional ISs kill target cells. These defects were more pronounced when lacking p66Shc, proapoptotic adaptor whose deficiency has been implicated aggressiveness both mouse model. Multiplex ELISA assays showed secrete abnormally elevated amounts CCL22, CCL24, IL-9 IL-10, which are further upregulated absence p66Shc. Among these, IL-10 also overexpressed patients, where they inversely correlated residual Using neutralizing antibodies recombinant cytokines show IL-9, but not mediates enhancement expression suppression effector functions CTLs. Our results demonstrate secreted negatively modulates anti-tumor immune abilities CTLs, highlighting new suppressive mechanism novel potential therapeutical

Язык: Английский

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID DOI Open Access
Pablo Gonzalez-Garcia, Ornella Fiorillo‐Moreno, Eloína Zarate Peñata

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 8290 - 8290

Опубликована: Май 5, 2023

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given diversity characteristic cellular phenotype, possible cytopathic, and clinical effects are difficult predict, determines heterogeneity COVID-19 symptoms. The purpose this article provide a comprehensive review cytopathic SARS-CoV-2 on cell types, focusing development COVID-19, may lead, some patients, persistence symptoms after recovery disease, condition known as long COVID. We describe mechanisms underlying virus-host interactions, including alterations protein expression, intracellular signaling pathways, immune responses. In particular, highlights potential impact these cytopathies function outcomes, such dysregulation, neuropsychiatric disorders, organ damage. concludes discussing future directions for research implications management treatment

Язык: Английский

Процитировано

16
Emerging roles of SARS-CoV-2 Spike-ACE2 in immune evasion and pathogenesis DOI Creative Commons
Cosima T. Baldari, Anna Onnis, Emanuele Andreano

и другие.

Trends in Immunology, Год журнала: 2023, Номер 44(6), С. 424 - 434

Опубликована: Апрель 6, 2023

The COVID-19 pandemic, caused by SARS-CoV-2, has an estimated 5 billion infections and 20 million deaths respiratory failure. In addition to the disease, SARS-CoV-2 infection been associated with many extrapulmonary complications not easily explainable infection. A recent study showed that spike protein, which mediates cell entry binding angiotensin-converting enzyme 2 (ACE2) receptor, signals through ACE2 change host behavior. CD8+ T cells, spike-dependent ACE2-mediated signaling suppresses immunological synapse (IS) formation impairs their killing ability, leading immune escape of virus-infected cells. this opinion article, we discuss consequences on response propose it contributes manifestations COVID-19.

Язык: Английский

Процитировано

14
From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID DOI Open Access
Pablo Gonzalez-Garcia, Ornella Fiorillo‐Moreno,

Eloina Zarate Peñate

и другие.

Опубликована: Март 30, 2023

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given diversity characteristic cellular phenotype, possible cytopathic, and clinical effects are difficult predict, determines heterogeneity COVID-19 symptoms. The purpose this article provide a comprehensive review cytopathic SARS-CoV-2 on cell types, focusing development COVID-19, may lead, some patients, persistence symptoms after recovery disease, condition known as long COVID. We describe mechanisms underlying virus-host interactions, including alterations protein expression, intracellular signaling pathways, immune responses. In particular, highlights potential impact these cytopathies function outcomes, such dysregulation, neuropsychiatric disorders, organ damage. concludes discussing future directions for research implications management treatment Long-COVID.

Язык: Английский

Процитировано

11
Leukemic cell-secreted interleukin-9 suppresses cytotoxic T cell-mediated killing in chronic lymphocytic leukemia DOI Creative Commons
Gioia Boncompagni, Vanessa Tatangelo, Ludovica Lopresti

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(2)

Опубликована: Фев. 15, 2024

Abstract The tumor microenvironment (TME) plays a central role in the pathogenesis of chronic lymphocytic leukemia (CLL), contributing to disease progression and chemoresistance. Leukemic cells shape TME into pro-survival immunosuppressive niche through contact-dependent contact-independent interactions with cellular components TME. Immune synapse (IS) formation is defective CLL. Here we asked whether soluble factors released by CLL contribute their protection from cytotoxic T cell (CTL)-mediated killing interfering this process. We found that healthy CTLs cultured media conditioned leukemic patients or Eμ-TCL1 mice upregulate exhaustion marker PD-1 become unable form functional ISs kill target cells. These defects were more pronounced when lacking p66Shc, proapoptotic adapter whose deficiency has been implicated aggressiveness both mouse model. Multiplex ELISA assays showed secrete abnormally elevated amounts CCL22, CCL24, IL-9 IL-10, which are further upregulated absence p66Shc. Among these, IL-10 also overexpressed patients, where they inversely correlated residual Using neutralizing antibodies recombinant cytokines show IL-9, but not mediates enhancement expression suppression effector functions CTLs. Our results demonstrate secreted negatively modulates anti-tumor immune abilities CTLs, highlighting new suppressive mechanism novel potential therapeutical

Язык: Английский

Процитировано

4
Antibody evasion associated with the RBD significant mutations in several emerging SARS-CoV-2 variants and its subvariants DOI
Manojit Bhattacharya, Srijan Chatterjee, Sang‐Soo Lee

и другие.

Drug Resistance Updates, Год журнала: 2023, Номер 71, С. 101008 - 101008

Опубликована: Сен. 22, 2023

Язык: Английский

Процитировано

10
Centrosome biogenesis and maintenance in homeostasis and disease DOI

Camila Fernandes-Mariano,

Joana N. Bugalhão, Diana Santos

и другие.

Current Opinion in Cell Biology, Год журнала: 2025, Номер 94, С. 102485 - 102485

Опубликована: Фев. 24, 2025

Язык: Английский

Процитировано

0
IFT20 regulates TFEB-dependent lytic granule biogenesis in cytotoxic T lymphocytes by orchestrating the MPR-dependent transport of granzyme B DOI Creative Commons
Francesca Finetti, Fabrizia Zevolini, Loredana Migliore

и другие.

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Май 19, 2025

Abstract Cytotoxic T lymphocytes (CTL) exploit specialized secretory lysosomes, the lytic granules (LG) to kill target cells. The LGs carry a battery of apoptosis-inducing molecules enriched in granzymes (GZM), perforin and FasL, which are released at immune synapse formed by CTLs with their cognate targets. Recent studies have revealed an unexpected diversity among LGs, suggesting existence multiple vesicular trafficking pathways biogenesis exocytosis. We previously implicated ciliary protein IFT20 retrograde cation-independent mannose-6-phosphate receptor (MPR), is required for lysosomal targeting acid hydrolases. Here we investigate role LG CTLs, showing that essential MPR recycling trans-Golgi network ensures proper granzyme B (GZMB) localization LGs. As result, deficiency impairs killing capability CTLs. In turn, rescue lysosome defects, IFT20-deficient expresses higher levels genes components cytotoxic machinery Interestingly, silico analysis suggests transcriptional co-regulation master regulator TFEB. Accordingly, modulation TFEB results alterations expression LG-related CTL-mediated cytotoxicity. Collectively, our identify as new player regulate highlight extended gene program regulated TFEB, downstream IFT20.

Язык: Английский

Процитировано

0
p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation DOI Creative Commons
Ludovica Lopresti, Nagaja Capitani, Vanessa Tatangelo

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Янв. 23, 2024

Introduction: Escape from immunosurveillance is a hallmark of chronic lymphocytic leukemia (CLL) cells. In the protective niche lymphoid organs, leukemic cells suppress ability T lymphocytes to form immune synapse (IS), thereby hampering T-cell mediated anti-tumoral activities. By binding its cognate receptor PD-1 at surface lymphocytes, inhibitory ligand PD-L1, which overexpressed in CLL cells, mediates suppressive activities However, molecular mechanism underlying PD-L1 overexpression remains unknown. We have previously reported defective expression pro-apoptotic and pro-oxidant adaptor p66Shc causally related an impairment intracellular reactive oxygen species (ROS) production activation ROS-sensitive transcription factor NF-κB. The fact that regulated by NF-κB suggests mechanistic relationship between deficiency Methods: 62 treatment-naive patients 43 healthy donors were included this study. was quantified B flow cytometry qRT-PCR. IS architecture local signaling assessed confocal microscopy. CD8+ cell killing activity cytometry. Results: Here we show residual isolated both mouse model Eμ-TCL1 inversely correlated with expression. also increase prevented forming ISs lymphocytes. Reconstitution p66Shc, but not ROS-defective mutant, CLL-derived line MEC-1, enhanced ROS decreased Similar results obtained following treatment H 2 O as exogenous source ROS, normalized recovered formation. Discussion: Our data provide direct evidence p66Shc-deficiency-related depletion concurs enhance provides basis for suppression cell-mediated functions immunosuppressive niche.

Язык: Английский

Процитировано

2
The possible mechanism and research progress of ACE2 involved in cardiovascular injury caused by COVID-19: a review DOI
Dan Luo,

Mengzhe Bai,

Wei Zhang

и другие.

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Май 27, 2024

ACE2 is the earliest receptor discovered to mediate entry of SARS-CoV-2. In addition receptor, it also participates in complex pathological and physiological processes, including regulating RAS system, apelin, KKS immune system. affecting respiratory viral infections interact with cardiovascular diseases. SARS-CoV-2 can directly invade system through ACE2; Similarly, diseases such as hypertension coronary heart disease affect levels exacerbate disease, dysregulation may be a potential mechanism for long-term acute sequelae COVID-19. Since SARS CoV-2 epidemic, many large population studies have tried clarify current focus debate, that is, whether we should give COVID-19 patients ACEI ARB drug treatment, but there still no conclusive conclusion. We discussed treatment options at present. Finally, researchers’ latest findings on their prospects future research.

Язык: Английский

Процитировано

2
Hypotensive drugs mitigate the high-sodium diet-induced pro-inflammatory activation of mouse macrophages in vivo DOI Open Access
Martyna Cieślik,

Spencer Strobel,

Paweł Bryniarski

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116648 - 116648

Опубликована: Апрель 26, 2024

Nowadays, there is an increasing emphasis on the need to alleviate chronic inflammatory response effectively treat hypertension. However, are still gaps in our understanding how achieve this. Therefore, research interaction of antihypertensive drugs with immune system extremely interesting, since their therapeutic effect could partly result from amelioration hypertension-related inflammation, which macrophages seem play a pivotal role. Thus, current comprehensive studies have investigated impact repeatedly administered hypotensive (captopril, olmesartan, propranolol, carvedilol, amlodipine, verapamil) macrophage functions innate and adaptive immunity, as well if drug-induced effects affected by high-sodium diet (HSD), one key environmental risk factors Although assayed medications increased generation reactive oxygen nitrogen intermediates standard fed donors, they reversed HSD-induced enhancing oxidative burst secretion pro-inflammatory cytokines. On other hand, some phagocytic activity expression surface markers involved antigen presentation, translated into enhanced ability activate B cells for antibody production. Moreover, augmented function effector phase contact hypersensitivity reaction, but suppressed sensitization cell-mediated under HSD conditions. Our findings contribute recognition mechanisms, excessive sodium intake affects hypertensive individuals, provide evidence that mitigate most adverse effects, suggesting additional protective activity.

Язык: Английский

Процитировано

1