Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-cells in the Context of HIV-1 infection DOI Open Access

Kim Doyon-Laliberté,

Matheus Aranguren,

Michelle Byrns

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Авг. 15, 2022

Abstract We have shown that excess B-cell activating factor (BAFF) in the blood of HIV-infected individuals, is concomitant with increased frequencies precursor-like marginal zone (MZp) B-cells, early on and despite successful antiretroviral therapy (ART). recently reported HIV-uninfected MZp possess a strong regulatory (Breg) potential. As such, B-cells highly express IL-10, orphan nuclear receptors (NR)4A1, NR4A2, NR4A3, molecule CD83, as well ectonucleotidases CD39 CD73, all which are associated regulation inflammation. Moreover, Breg function involves CD83 signals. Herein, order to address impact HIV infection excessive BAFF environment their capacities, we performed transcriptomic analyses by RNA-seq sorted from progressors. The profile progressors were assessed flow-cytometry light microscopy high content screening (HCS) analyses, respectively. In addition, effects controls investigated vitro . report significant downregulation NR4A1, NR4A3 gene transcripts when compared controls. protein expression levels also downregulated not restored ART. observe decreased IL-10 tonsillar individuals following treatment BAFF, significantly diminished function. These findings suggest contributes alteration potential could lead loss “immune surveillance”, during possibly other situations where found excess. Author Summary population, previously described human tonsils, presents an important “Breg” potential, depicted elevated receptor (NR)4As levels, similarly Tregs, our knowledge currently underexplored studies. present chronic inflammatory context such HIV-infection, its environment, may exert capacities MZp, both ex vivo , affecting NR4As growing significance, especially importance MZ NR4A1 atherosclerosis immune surveillance. finding surveillance be altered circumstances inflammation pivotal interest, treated often prematurely develop co-morbidities aging cardiovascular diseases (CVD). has been several autoimmune contexts CVD leading cause death.

Язык: Английский

B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine DOI Creative Commons

Antonio Cembellin-Prieto,

Zheng Luo,

Heather Kulaga

и другие.

Nature Immunology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Abstract The rapid onset of innate immune defenses is critical for early control viral replication in an infected host and yet it can also lead to irreversible tissue damage, especially the respiratory tract. Sensitive regulators must exist that modulate inflammation, while controlling infection. In present study, we identified acetylcholine (ACh)-producing B cells as such regulators. are most prevalent ACh-producing leukocyte population tract demonstrated with choline acetyltransferase (ChAT)-green fluorescent protein (GFP) reporter mice, both before after infection influenza A virus. Mice lacking ChAT cells, disabling their ability generate ACh (ChatBKO), but not those T significantly, selectively directly suppressed α7-nicotinic-ACh receptor-expressing interstitial, alveolar, macrophage activation secrete tumor necrosis factor (TNF), better virus at 1 d postinfection. Conversely, TNF blockade via monoclonal antibody treatment increased loads time. By day 10 infection, ChatBKO mice showed local systemic inflammation reduced signs lung epithelial repair despite similar clearance. Thus, key participants immediate regulatory cascade controls damage shifting balance toward cost enhanced replication.

Язык: Английский

Процитировано

2
Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade DOI Creative Commons
Akshay J. Patel, Zena Willsmore, Naeem Khan

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 7, 2022

Abstract Checkpoint blockade with Pembrolizumab, has demonstrated durable clinical responses in advanced non-small cell lung cancer, however, treatment is offset by the development of high-grade immune related adverse events (irAEs) some patients. Here, we show that these patients a deficient Breg checkpoint fails to limit self-reactive T enhanced activity and auto-antibody formation enabled PD-1/PD-L1 blockade, leading severe auto-inflammatory sequelae. Principally failure IL-10 producing regulatory B cells as through functional ex vivo assays deep phenotyping mass cytometric analysis, major significant finding who develop irAEs when undergoing anti-PD1/PD-L1 blockade. There currently lack biomarkers identify priori those at greatest risk developing syndrome. Pre-therapy profiling could provide an important tool cancer high on

Язык: Английский

Процитировано

36
Diabetic complications and prospective immunotherapy DOI Creative Commons

Lewis Reynolds,

Zhengkang Luo, K. N. Singh

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 7, 2023

The incidence of Diabetes Mellitus is increasing globally. Individuals who have been burdened with diabetes for many years often develop complications as a result hyperglycemia. More and more research being conducted highlighting inflammation an important factor in disease progression. In all kinds diabetes, hyperglycemia leads to activation alternative glucose metabolic pathways, resulting problematic by-products including reactive oxygen species advanced glycation end products. This review takes look into the pathogenesis three specific diabetic complications; retinopathy, nephropathy neuropathy well their current treatment options. By considering recent papers investigating effects immunotherapy on relevant conditions animal models, multiple strategies are suggested future prevention emphasis molecular targets associated inflammation.

Язык: Английский

Процитировано

23
Pathogenesis of rheumatoid arthritis: one year in review 2023 DOI Open Access
Francesco Mariani, Irene Martelli,

Francesca Pistone

и другие.

Clinical and Experimental Rheumatology, Год журнала: 2023, Номер unknown

Опубликована: Июнь 19, 2023

Язык: Английский

Процитировано

19
Compromised anti-osteoclastogenic and immunomodulatory functions of regulatory B cells (Bregs) aggravate inflammatory bone loss in post-menopausal osteoporosis DOI
Leena Sapra, Chaman Saini, Pradyumna Kumar Mishra

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер unknown, С. 167675 - 167675

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

1
Regulation of CD8 T cell by B-cells: A narrative review DOI Creative Commons
Tess Van Meerhaeghe, A. Néel, Sophie Brouard

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 8, 2023

Activation of CD4 T cells by B has been extensively studied, but cell-regulated priming, proliferation, and survival CD8 remains controversial. express high levels MHC class I molecules can potentially act as antigen-presenting (APCs) for cells. Several in vivo studies mice humans demonstrate the role modulators cell function context viral infections, autoimmune diseases, cancer allograft rejection. In addition, B-cell depletion therapies lead to impaired T-cell responses. this review, we attempt answer 2 important questions: 1. antigen presentation cytokine production regulation fate determination, 2. The formation maintenance memory.

Язык: Английский

Процитировано

14
B cell heterogeneity, plasticity, and functional diversity in cancer microenvironments DOI
Wei Yuan, Chun-Xiang Huang, Christos Xiao

и другие.

Oncogene, Год журнала: 2021, Номер 40(29), С. 4737 - 4745

Опубликована: Июнь 29, 2021

Язык: Английский

Процитировано

32
Inflammation and immunomodulation in central nervous system injury – B cells as a novel therapeutic opportunity DOI Creative Commons
Saumya Maheshwari, Liam Dwyer, Ruxandra F. Sîrbulescu

и другие.

Neurobiology of Disease, Год журнала: 2023, Номер 180, С. 106077 - 106077

Опубликована: Март 11, 2023

Acute injury to the central nervous system (CNS) remains a complex and challenging clinical need. CNS initiates dynamic neuroinflammatory response, mediated by both resident infiltrating immune cells. Following primary injury, dysregulated inflammatory cascades have been implicated in sustaining pro-inflammatory microenvironment, driving secondary neurodegeneration development of lasting neurological dysfunction. Due multifaceted nature clinically effective therapies for conditions such as traumatic brain (TBI), spinal cord (SCI), stroke proven develop. No therapeutics that adequately address chronic component are currently available. Recently, B lymphocytes gained increasing appreciation their role maintaining homeostasis regulating responses context tissue injury. Here we review response with particular focus on underexplored cells summarize recent results use purified novel immunomodulatory therapeutic particularly CNS.

Язык: Английский

Процитировано

13
Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus DOI Creative Commons
Yi‐Giien Tsai, P. F. Liao,

Kai‐Hung Hsiao

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Сен. 12, 2023

Systemic lupus erythematosus (SLE) is a heterogeneous multisystem inflammatory disease with wide variability in clinical manifestations. Natural arising CD4+ regulatory T cells (Tregs) play critical role maintaining peripheral tolerance by suppressing inflammation and preventing autoimmune responses SLE. Additionally, CD8+ cells, type 1 (Tr1), B also have less well-defined the pathogenesis of Elucidation roles various Treg subsets dedicated to immune homeostasis will provide novel therapeutic approach that governs for remission active lupus. Diminished interleukin (IL)-2 production associated depleted cell population, its reversibility IL-2 therapy provides important reasons treatment This review focuses on new therapeutics human low-dose benefits

Язык: Английский

Процитировано

13
Tolerogenic dendritic cells in type 1 diabetes: no longer a concept DOI Creative Commons
Nick Giannoukakis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июнь 14, 2023

Tolerogenic dendritic cells (tDC) arrest the progression of autoimmune-driven dysglycemia into clinical, insulin-requiring type 1 diabetes (T1D) and preserve a critical mass β able to restore some degree normoglycemia in new-onset clinical disease. The safety tDC, generated ex vivo from peripheral blood leukocytes, has been demonstrated phase I studies. Accumulating evidence shows that tDC act via multiple layers immune regulation arresting action pancreatic cell-targeting effector lymphocytes. share number phenotypes mechanisms action, independent method by which they are . In context safety, this yields confidence time come test best characterized II trials T1D, especially given already being tested for other autoimmune conditions. is also now refine purity markers “universalize” methods generated. This review summarizes current state therapy presents points intersection different embodiments use induce tolerance, offers insights outstanding matters address as studies imminent. Finally, we present proposal co-administration serially-alternating administration T-regulatory (Tregs) synergistic complementary approach prevent treat T1D.

Язык: Английский

Процитировано

12