IRG1/itaconate enhances efferocytosis by activating Nrf2-TIM4 signaling pathway to alleviate con A induced autoimmune liver injury DOI Creative Commons

Liwu Zeng,

Yaxin Wang,

Yongzhou Huang

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 5, 2025

Immune response gene 1 (IRG1) is highly expressed in mitochondria of macrophages a pro-inflammatory state. IRG1 and its metabolites play important roles infection, immune-related diseases tumor progression by exerting resistance pathogens, attenuating inflammation producing antioxidant substances through various pathways mechanisms. deficiency aggravates liver injury. Efferocytosis vital mechanism for preventing the inflammatory tissue damage. However, how IRG1/itaconate regulates efferocytosis autoimmune hepatitis has yet to be fully understood. Therefore, we explored influence IRG1-/- on effects regulating nuclear factor erythroid 2-associated 2 (Nrf2)-T-cell immunoglobulin domain mucin 4 (TIM4) pathway An model was established injecting Con A into wild-type mice via tail vein. Liver injury were assessed. The role potential regulatory mechanisms also analysed. Exogenous 4-octyl itaconate (OI) supplementation promoted expression Nrf2 TIM4 restored bone marrow-derived macrophage (BMDM) efferocytosis, whereas inhibition mediated ML385 led impaired BMDMs, decreased TIM4, aggravated Additionally, after supplementing Nrf2-/- BMDMs with exogenous OI, evaluated changes effect, did not change, protective effect OI disappeared. when blocked, efferocytotic attenuated, oxidative stress aggravated. transformation M2 macrophages, this inhibited blocked. To our best understanding, initial exploration show that downstream molecule IRG1/itaconate-Nrf2 pathway, efferocytosis. These findings suggest new treatment promoting resolution hepatitis.

Language: Английский

Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies DOI
Manu Shankar‐Hari, Thierry Calandra, Miguel P. Soares

et al.

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: 12(4), P. 323 - 336

Published: Feb. 23, 2024

Language: Английский

Citations

34
Arterial Stiffness: From Basic Primers to Integrative Physiology DOI Creative Commons
Véronique Regnault, Patrick Lacolley, Stéphane Laurent

et al.

Annual Review of Physiology, Journal Year: 2024, Volume and Issue: 86(1), P. 99 - 121

Published: Feb. 12, 2024

The elastic properties of conductance arteries are one the most important hemodynamic functions in body, and data continue to emerge regarding importance their dysfunction vascular aging a range cardiovascular diseases. Here, we provide new insight into integrative physiology arterial stiffening its clinical consequence. We also comprehensively review progress made on pathways/molecules that appear today as basic determinants stiffness, particularly those mediating smooth muscle cell (VSMC) contractility, plasticity stiffness. focus membrane nuclear mechanotransduction, clearance function wall, phenotypic switching VSMCs, immunoinflammatory stimuli epigenetic mechanisms. Finally, discuss advances latest studies revisit classical therapeutic concepts stiffness lead patient-by-patient strategy according risk exposure underlying disease.

Language: Английский

Citations

18
Trained immunity in atherosclerotic cardiovascular disease DOI
Niels P. Riksen, Siroon Bekkering, Willem J. M. Mulder

et al.

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(12), P. 799 - 811

Published: June 15, 2023

Language: Английский

Citations

41
Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives DOI Creative Commons

Cuiqing Huang,

Ni Shao,

Yanyu Huang

et al.

Materials Today Bio, Journal Year: 2023, Volume and Issue: 23, P. 100839 - 100839

Published: Oct. 21, 2023

STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field cancer immunotherapy, owing to their excellent capacity activate innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration strategies employed develop effective formulations for agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements delivery systems based lipids, natural/synthetic polymers, proteins are summarized. preparation methodologies nanoprecipitation, self-assembly, hydrogel, along advantages disadvantages, also discussed. Furthermore, challenges opportunities developing next-generation agonist elaborated. aims serve reference researchers designing novel immunotherapy.

Language: Английский

Citations

37
Trained immunity: Target for prophylaxis and therapy DOI

Athanasios Ziogas,

Mariolina Bruno, Roy van der Meel

et al.

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(11), P. 1776 - 1791

Published: Nov. 1, 2023

Language: Английский

Citations

28
Innate immune memory in cardiometabolic disease DOI Creative Commons
Harsh Bahrar, Siroon Bekkering, Rinke Stienstra

et al.

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 119(18), P. 2774 - 2786

Published: Feb. 16, 2023

Abstract Low-grade systemic inflammation is a key pathophysiological component of atherosclerotic cardiovascular disease (CVD), and long-term activation myeloid cells thought to be crucial for these effects. Obesity associated metabolic complications including hyperglycaemia dyslipoproteinaemia can induce long-lasting inflammatory reprogramming the innate immune their bone marrow progenitors, which in turn contributes atherosclerosis. In this review, we discuss mechanisms through undergo changes functional, epigenetic, characteristics upon even short-term exposure endogenous ligands, process also termed ‘trained immunity’. Inappropriate induction trained immunity leads development hyperinflammatory proatherogenic monocytes macrophages, an important factor atherosclerosis CVDs. Knowledge specific distinct intracellular molecular pathways involved will reveal novel pharmacological targets that could used prevent or treat CVDs future.

Language: Английский

Citations

23
The causes and consequences of trained immunity in myeloid cells DOI Creative Commons
Gunapati Bhargavi, Selvakumar Subbian

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 11, 2024

Conventionally, immunity in humans has been classified as innate and adaptive, with the concept that only latter type an immunological memory/recall response against specific antigens or pathogens. Recently, a new of trained (a.k.a. memory response) emerged. According to this concept, immune cells can exhibit enhanced responsiveness subsequent challenges, after initial stimulation antigen/pathogen. Thus, enables respond robustly non-specifically through exposure re-exposure antigens/infections vaccines, providing resistance unrelated pathogens reduced infection severity. For example, individuals vaccinated BCG protect tuberculosis were also protected from malaria SARS-CoV-2 infections. Epigenetic modifications such histone acetylation metabolic reprogramming (e.g. shift towards glycolysis) their inter-linked regulations are key factors underpinning activation cells. The integrated epigenetic rewiring generates sufficient intermediates, which is crucial meet energy demand required produce proinflammatory antimicrobial responses by These determine efficacy durability immunity. Importantly, signaling pathways regulatory molecules be harnessed potential targets for developing novel intervention strategies, better vaccines immunotherapies infectious (e.g., sepsis) non-infectious cancer) diseases. However, aberrant inflammation caused inappropriate onset lead severe autoimmune pathological consequences, systemic sclerosis granulomatosis). In review, we provide overview conventional adaptive summarize various mechanistic associated regulation immunity, focusing on immunologic, metabolic, changes myeloid This review underscores transformative immunology, paving way therapeutic strategies diseases leverage memory.

Language: Английский

Citations

10
Friends to remember: innate immune memory regulation by the microbiota DOI Creative Commons
Aize Pellón, Ainhoa Palacios, Leticia Abecia

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Training vs. Tolerance: The Yin/Yang of the Innate Immune System DOI Creative Commons
Trim Lajqi, Natascha Köstlin‐Gille, Reinhard Bauer

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 766 - 766

Published: March 2, 2023

For almost nearly a century, memory functions have been attributed only to acquired immune cells. Lately, this paradigm has challenged by an increasing number of studies revealing that innate cells are capable exhibiting memory-like features resulting in increased responsiveness subsequent challenges, process known as trained immunity (known also memory). In contrast, the refractory state endotoxin tolerance defined immunosuppressive myeloid portrayed significant reduction inflammatory capacity. Both training well adaptive reported be accompanied epigenetic and metabolic alterations occurring While conveys proper protection against secondary infections, induction promotes repairing mechanisms Consequently, inappropriate these cues may trigger maladaptive effects, promoting susceptibility infections—tolerance, or contribute progression disorder—trained immunity. This review aims at discussion opposing manners non-immune cells, describing molecular, involved interpreting clinical implications various pathologies.

Language: Английский

Citations

19
Genetic and epigenetic dysregulation of innate immune mechanisms in autoinflammatory diseases DOI Creative Commons
Laura M. Merlo Pich,

Athanasios Ziogas,

Mihai G. Netea

et al.

FEBS Journal, Journal Year: 2024, Volume and Issue: 291(20), P. 4414 - 4432

Published: March 12, 2024

Dysregulation and hyperactivation of innate immune responses can lead to the onset systemic autoinflammatory diseases. Monogenic diseases are caused by inborn genetic errors based on molecular mechanisms at play, be divided into inflammasomopathies, interferonopathies, relopathies, protein misfolding, endogenous antagonist deficiencies. On other hand, more common multifactorial, with both non‐genetic factors playing an important role. During last decade, long‐term memory characteristics have been described (also called trained immunity) that in physiological conditions provide enhanced host protection from pathogenic re‐infection. However, if dysregulated, induction immunity become maladaptive, perpetuating chronic inflammatory activation. Here, we describe epigenetic dysregulation system maladaptive leads perpetuation most recently

Language: Английский

Citations

7