Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis DOI
Ruxandra F. Sîrbulescu,

Katharine Nicholson,

Kento Kawai

и другие.

The FASEB Journal, Год журнала: 2024, Номер 38(13)

Опубликована: Июль 5, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes murine models skin brain injury through a process termed pligodraxis, which adopt immunoregulatory neuroprotective phenotype injured environment. Here, we investigated effects B‐cell therapy SOD1 G93A mouse model person living with ALS. Purified splenic mature naïve from haploidentical donor mice were administered intravenously for total 10 weekly doses. For clinical study advanced ALS, IgA gammopathy unclear significance, lymphopenia, CD19 + positively selected healthy infused twice, at 60‐day interval. Repeated intravenous was safe significantly delayed disease onset, extended survival, reduced cellular apoptosis, decreased astrogliosis mice. infusion did not appear to generate clinically evident inflammatory response. An improvement 5 points on ALSFRS‐R scale observed after first infusion. Levels markers showed persistent reduction post‐infusion. This represents demonstration efficacy safety feasibility using purified lymphocytes as cell‐based therapeutic strategy

Язык: Английский

Traumatic brain injury alters the effects of class II invariant peptide (CLIP) antagonism on chronic meningeal CLIP + B cells, neuropathology, and neurobehavioral impairment in 5xFAD mice DOI Creative Commons
Jaclyn Iannucci,

Reagan Dominy,

Shreya Bandopadhyay

и другие.

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Июнь 27, 2024

Abstract Background Traumatic brain injury (TBI) is a significant risk factor for Alzheimer’s disease (AD), and accumulating evidence supports role adaptive immune B T cells in both TBI AD pathogenesis. We previously identified cell major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive expansion after TBI. also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII acutely reduced + splenic was neuroprotective. The current study investigated chronic effects 5xFAD mouse model, with without Methods 12-week-old male wild type (WT) mice were administered either antagonist (CAP) or vehicle, once at 30 min sham lateral fluid percussion (FPI). Analyses included flow cytometric analysis dural meninges spleen, histopathological brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, assessment motor neurobehavioral function over ensuing 6 months. Results 9-month-old had significantly more compared age-matched WT mice. A one-time treatment CAP this population Importantly, improved some immune, histopathological, impairments six Although FPI did not further elevate meningeal cells, it negate ability reduce 3 months age exacerbated aspects pathology mice, including reducing hippocampal neurogenesis, increasing plaque deposition CA3, altering microgliosis, disrupting structure. ameliorated but all these effects.

Язык: Английский

Процитировано

6

Intruders or protectors – the multifaceted role of B cells in CNS disorders DOI Creative Commons

James W. Aspden,

Matthew A. Murphy,

Rommi D. Kashlan

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Янв. 10, 2024

B lymphocytes are immune cells studied predominantly in the context of peripheral humoral responses against pathogens. Evidence has been accumulating recent years on diversity immunomodulatory functions that undertake, with particular relevance for pathologies central nervous system (CNS). This review summarizes current knowledge cell populations, localization, infiltration mechanisms, and function CNS associated tissues. Acute chronic neurodegenerative examined order to explore complex, sometimes conflicting, effects can have each context, implications disease progression treatment outcomes. Additional factors such as aging modulate proportions subpopulations over time also discussed neuroinflammatory response susceptibility. A better understanding multifactorial role populations may ultimately lead innovative therapeutic strategies a variety neurological conditions.

Язык: Английский

Процитировано

5

The cross-talk between B cells and macrophages DOI Creative Commons

Yahui Su,

Siyi Liu, Chen Long

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113463 - 113463

Опубликована: Окт. 30, 2024

Язык: Английский

Процитировано

5

B cells in non-lymphoid tissues DOI
Abrar Samiea,

George Celis,

Rashi Yadav

и другие.

Nature reviews. Immunology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Язык: Английский

Процитировано

0

SIV-specific antibodies protect against inflammasome-driven encephalitis in untreated macaques DOI Creative Commons

Natalie Castell,

Celina Monteiro Abreu,

Erin N. Shirk

и другие.

Cell Reports, Год журнала: 2024, Номер 43(10), С. 114833 - 114833

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

2

Elucidating the neuroimmunology of traumatic brain injury: methodological approaches to unravel intercellular communication and function DOI Creative Commons
Hadi Abou‐El‐Hassan, Joshua D. Bernstock, Joshua I. Chalif

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Дек. 13, 2023

The neuroimmunology of traumatic brain injury (TBI) has recently gained recognition as a crucial element in the secondary pathophysiological consequences that occur following neurotrauma. Both immune cells residing within central nervous system (CNS) and those migrating from periphery play significant roles development injury. However, precise mechanisms governing communication between innate adaptive remain incompletely understood, partly due to limited utilization relevant experimental models techniques. Therefore, this discussion, we outline current methodologies can aid exploration TBI neuroimmunology, with particular emphasis on interactions resident neuroglial recruited lymphocytes. These techniques encompass adoptive cell transfer, intra-CNS injection(s), selective cellular depletion, genetic manipulation, molecular neuroimaging, well vitro co-culture systems organoid models. By incorporating key elements both immunity, these methods facilitate examination clinically interactions. In addition preclinical approaches, also detail an emerging avenue research seeks leverage human biofluids. This approach enables investigation how infiltrating modulate responses after TBI. Considering growing significance neuroinflammation TBI, introduction application advanced will be pivotal advancing translational field.

Язык: Английский

Процитировано

1

Comparative analysis of meningeal transcriptomes in birds: Potential pathways of resilience to repeated impacts DOI
Abby E. Beatty,

Tara M. Barnes‐Tompkins,

Kira M. Long

и другие.

The Anatomical Record, Год журнала: 2024, Номер unknown

Опубликована: Окт. 8, 2024

Abstract The meninges and associated vasculature (MAV) play a crucial role in maintaining cerebral integrity homeostasis. Recent advances transcriptomic analysis have illuminated the significance of MAV understanding complex physiological interactions at interface between skull brain after exposure to mechanical stress. To investigate how responses may confer resilience against repetitive stress, we performed first avian tissues using Downy Woodpecker ( Dryobates pubescens ) Tufted Titmouse Baeolophus bicolor as comparison species. Our findings reveal divergences gene expression profiles related immune response, cellular stress management, protein translation machinery. male woodpeckers exhibit tailored modulation strategy that potentially dampens neuroinflammation while preserving protective immunity. Overrepresented genes involved suggest enhanced mechanisms for mitigating damage promoting repair. Additionally, enrichment translation‐associated pathways hints increased capacity turnover remodeling vital recovery. study not only fills critical gap neurobiology but also lays groundwork research comparative neuroprotection.

Язык: Английский

Процитировано

0

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features DOI Creative Commons
Nathalie Bendriss‐Vermare, Valentin Picant,

Lara Revol-Bauz

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 19, 2024

Abstract Natural Killer (NK) cells lose their effector functions towards dangerous in chronic inflammatory diseases through still elusive mechanisms. Here, we demonstrate that Interleukin 35 (IL-35), an immunosuppressive member of the IL-12 family, inhibits human NK cell proliferation, pro-inflammatory, and cytotoxic functions, while promoting secretion TGF-β proangiogenic factors. Furthermore, prolonged exposure to IL-35 converts into ILC1-like with tissue residency features (CD9 + CD103 CD49a ) low was dependent on autocrine TGF-β. Single RNAseq analysis also revealed heterogeneity associated initial subpopulation, conventional or adaptive, undergoing conversion. Overall, our findings identify a new role as key driver plasticity leading acquisition weakened might play physiopathological contexts represent attractive target for future immunotherapies improve clinical activity.

Язык: Английский

Процитировано

0

Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis DOI
Ruxandra F. Sîrbulescu,

Katharine Nicholson,

Kento Kawai

и другие.

The FASEB Journal, Год журнала: 2024, Номер 38(13)

Опубликована: Июль 5, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes murine models skin brain injury through a process termed pligodraxis, which adopt immunoregulatory neuroprotective phenotype injured environment. Here, we investigated effects B‐cell therapy SOD1 G93A mouse model person living with ALS. Purified splenic mature naïve from haploidentical donor mice were administered intravenously for total 10 weekly doses. For clinical study advanced ALS, IgA gammopathy unclear significance, lymphopenia, CD19 + positively selected healthy infused twice, at 60‐day interval. Repeated intravenous was safe significantly delayed disease onset, extended survival, reduced cellular apoptosis, decreased astrogliosis mice. infusion did not appear to generate clinically evident inflammatory response. An improvement 5 points on ALSFRS‐R scale observed after first infusion. Levels markers showed persistent reduction post‐infusion. This represents demonstration efficacy safety feasibility using purified lymphocytes as cell‐based therapeutic strategy

Язык: Английский

Процитировано

0