Destabilisation of T cell-dependent humoral immunity in sepsis DOI Creative Commons
Kate Davies, James E. McLaren

Clinical Science, Journal Year: 2024, Volume and Issue: 138(1), P. 65 - 85

Published: Jan. 1, 2024

Abstract Sepsis is a heterogeneous condition defined as life-threatening organ dysfunction caused by dysregulated host response to infection. For some, sepsis presents predominantly suppressive disorder, whilst others experience pro-inflammatory which can culminate in ‘cytokine storm’. Frequently, patients signs of concurrent hyper-inflammation and immunosuppression, underpinning the difficulty directing effective treatment. Although intensive care unit mortality rates have improved recent years, one-third discharged die within following year. Half post-sepsis deaths are due exacerbation pre-existing conditions, half complications arising from deteriorated immune system. It has been suggested that intense infection may induce irreversible metabolic reprogramming cells. As critical arm protection vertebrates, alterations adaptive system devastating repercussions. Indeed, marked depletion lymphocytes observed sepsis, correlating with increased mortality. Such sepsis-induced lymphopenia profound consequences on how T cells respond but equally humoral both elicited B supported distinct CD4+ follicular helper (TFH) cell subsets. The immunosuppressive state further exacerbated functional impairments remaining lymphocyte population, including presence expressing dysfunctional or exhausted phenotypes. This review will specifically focus destabilises system, closer examination TFH affected corresponding impact immunity.

Language: Английский

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits DOI Creative Commons
Moritz Peiseler, Robert F. Schwabe, Jochen Hampe

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

Citations

303
TGF-β signaling in health, disease and therapeutics DOI Creative Commons

Ziqin Deng,

Tao Fan, Xiao Chu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 22, 2024

Abstract Transforming growth factor (TGF)-β is a multifunctional cytokine expressed by almost every tissue and cell type. The signal transduction of TGF-β can stimulate diverse cellular responses particularly critical to embryonic development, wound healing, homeostasis, immune homeostasis in health. dysfunction play key roles many diseases, numerous targeted therapies have been developed rectify its pathogenic activity. In the past decades, large number studies on signaling carried out, covering broad spectrum topics health, disease, therapeutics. Thus, comprehensive overview required for general picture this field. review, we retrace research history introduce molecular mechanisms regarding biosynthesis, activation, transduction. We also provide deep insights into functions physiological conditions as well pathological processes. TGF-β-targeting which brought fresh hope treatment relevant diseases are highlighted. Through summary previous knowledge recent updates, review aims systematic understanding attract more attention interest area.

Language: Английский

Citations

211
CD39/CD73/A2AR pathway and cancer immunotherapy DOI Creative Commons

Chenglai Xia,

Shuanghong Yin,

Kenneth K.W. To

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 2, 2023

Abstract Cancer development is closely associated with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes cell immunologic escape. The sequential conversion of extracellular ATP into adenosine by two important cell-surface ectonucleosidases CD39 CD73 play critical roles in reshaping an TME. accumulated mediates its regulatory functions binding to one four receptors (A1R, A2AR, A2BR A3R). A2AR elicits profound function via regulating cAMP signaling. increasing evidence suggests CD39, could be used as novel therapeutic targets for manipulating the immunity. In recent years, monoclonal antibodies or small molecule inhibitors targeting CD39/CD73/A2AR pathway have been investigated clinical trials single agents combination anti-PD-1/PD-L1 therapies. this review, we provide updated summary about pathophysiological adenosinergic cancer development, metastasis drug resistance. more components therapy circumvention immunotherapy resistance are also discussed. Emerging biomarkers may guide selection CD39/CD73/A2AR-targeting treatment strategies individual patients deliberated.

Language: Английский

Citations

143
Estrogen Receptor Signaling in the Immune System DOI Open Access
Binita Chakraborty, Jovita Byemerwa,

Taylor Krebs

et al.

Endocrine Reviews, Journal Year: 2022, Volume and Issue: 44(1), P. 117 - 141

Published: June 16, 2022

The immune system functions in a sexually dimorphic manner, with females exhibiting more robust responses than males. However, how female sex hormones affect function normal homeostasis and autoimmunity is poorly understood. In this review, we discuss estrogens innate adaptive cell activity dysregulation of estrogen signaling underlies the pathobiology some autoimmune diseases cancers. potential roles major circulating estrogens, each 3 receptors (ERα, ERβ, G-protein coupled receptor) regulation different cells are considered. This provides framework for discussion impact ER modulators (aromatase inhibitors, selective receptor modulators, downregulators) on immunity. Synthesis information timely given considerable interest late defining mechanistic basis sex-biased responses/outcomes patients cancers treated checkpoint blockade. It will also be instructive respect to further development that modulate immunity therapeutically useful manner.

Language: Английский

Citations

113
The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited DOI Open Access
Kevin Dzobo,

Dimakatso Alice Senthebane,

Collet Dandara

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(2), P. 376 - 376

Published: Jan. 6, 2023

Tumorigenesis is a complex and dynamic process involving cell-cell cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance metastasis. This review provides an updated summary of the role played by microenvironment (TME) components hypoxia in tumorigenesis, highlight various ways through which cells reprogram normal into phenotypes are pro-tumorigenic, including cancer associated- fibroblasts, -macrophages -endothelial cells. Tumor secrete numerous factors leading to transformation previously anti-tumorigenic environment pro-tumorigenic environment. Once formed, solid tumors continue interact with stromal cells, local infiltrating macrophages, mesenchymal stem endothelial pericytes, secreted ECM within (TME). The TME key response treatment outcome. Importantly, can initially be anti-tumorigenic, but over time promote tumorigenesis induce therapy resistance. To counter hypoxia, increased angiogenesis leads formation new vascular networks order actively sustain growth via supply oxygen nutrients, whilst removing metabolic waste. Angiogenic network aid metastatic dissemination. Successful novel development require identification therapeutic targeting cancer-associated- fibroblasts (CAFs) (CAMs), blocking ECM-receptor interactions, addition reprogramming immune success. Lastly, this highlights potential TME- hypoxia-centered therapies under investigation.

Language: Английский

Citations

94
Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment DOI Open Access
Mengdan Xu, Shenglong Li

Cancer Letters, Journal Year: 2023, Volume and Issue: 574, P. 216397 - 216397

Published: Sept. 18, 2023

Language: Английский

Citations

64
Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering DOI Creative Commons
Xiao Xu, Limei Xu, Jiang Xia

et al.

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 168, P. 372 - 387

Published: July 21, 2023

Osteoarthritis (OA) is a widespread clinical disease characterized by cartilage degeneration in middle-aged and elderly people. Currently, there no effective treatment for OA apart from total joint replacement advanced stages. Mesenchymal stem cells (MSCs) are type of adult cell with diverse differentiation capabilities immunomodulatory potentials. MSCs known to effectively regulate the microenvironment, promote regeneration, alleviate symptoms. As result, they promising sources therapy. Recent studies have revealed presence resident synovial fluid, membrane, articular cartilage, which can be collected as knee joint-derived (KJD-MSC). Several preclinical demonstrated that KJD-MSCs great potential treatment, whether applied alone, combination biomaterials, or exocrine MSCs. In this article, we will review characteristics joints, including their cytological characteristics, such proliferation, differentiation, abilities, well biological function MSC exosomes. We also discuss use tissue engineering introduce concept new generation cell-based therapy, engineering, gene editing techniques create KJD-MSC derivative exosomes improved functionality targeted delivery. These advances aim maximize efficiency provide strategies overcome bottleneck This research insights into medicinal benefit Joint Stem Cells (MSCs), specifically on its ability. Through review, community further realize promoting mesenchymal cells, especially progenitor/MSC-like progenitor (CPSC), preventive measure against osteoarthritis injury. People medical institutions may consider derived an alternative approach degeneration. Moreover, discussion presented study convey valuable information future explore benefits MSC.

Language: Английский

Citations

43
Regulatory B Cells—Immunopathological and Prognostic Potential in Humans DOI Creative Commons

Johanna Veh,

Carolin Ludwig, Hubert Schrezenmeier

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(4), P. 357 - 357

Published: Feb. 18, 2024

The aim of the following review is to shed light on putative role regulatory B cells (Bregs) in various human diseases and highlight their potential prognostic therapeutic relevance humans. Regulatory are a heterogeneous group lymphocytes capable suppressing inflammatory immune reactions. In this way, Bregs contribute maintenance tolerance homeostasis by limiting ongoing reactions temporally spatially. play an important attenuating pathological that can be associated with transplant rejection, graft-versus-host disease, autoimmune allergies but also infectious, neoplastic metabolic diseases. Early studies identified IL-10 as functional molecule, so IL-10-secreting murine B10 cell still considered prototype Breg, has long been central search for Breg equivalents. However, over past two decades, other molecules may immunosuppressive function have discovered, some which only present Bregs. This expanded arsenal includes several anti-inflammatory cytokines, such IL-35 TGF-β, enzymes CD39/CD73, granzyme IDO well surface proteins including PD-L1, CD1d CD25. summary, illustrates concise comprehensive manner although share common features leading prominent immunpathologies, they composed pool different types rather phenotypic transcriptional properties.

Language: Английский

Citations

16
Human IL-10-producing B cells have diverse states that are induced from multiple B cell subsets DOI Creative Commons
Marla C. Glass, David R. Glass,

John-Paul Oliveria

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 39(3), P. 110728 - 110728

Published: April 1, 2022

Regulatory B cells (Bregs) suppress immune responses through the secretion of interleukin-10 (IL-10). This immunomodulatory capacity holds therapeutic potential, yet a definitional immunophenotype for enumeration and prospective isolation capable IL-10 production remains elusive. Here, we simultaneously quantify cytokine in human peripheral across range stimulatory conditions time points using mass cytometry. Our analysis shows that multiple functional cell subsets produce no phenotype uniquely identifies IL-10+ cells. Further, significant portion co-express pro-inflammatory cytokines IL-6 tumor necrosis factor alpha (TNFα). Despite this heterogeneity, operationally tolerant liver transplant recipients have unique enrichment IL-10+, but not TNFα+ or IL-6+, compared with receiving immunosuppression. Thus, IL-10-producing constitute an induced, transient state arising from diversity may contribute to maintenance homeostasis.

Language: Английский

Citations

54
Cytokine production by human B cells: role in health and autoimmune disease DOI Creative Commons
Nina M. de Gruijter, Bethany R. Jebson, Elizabeth C. Rosser

et al.

Clinical & Experimental Immunology, Journal Year: 2022, Volume and Issue: 210(3), P. 253 - 262

Published: Sept. 30, 2022

B cells are classically considered solely as antibody-producing driving humoral immune responses to foreign antigens in infections and vaccinations well self-antigens pathological settings such autoimmunity. However, it has now become clear that can also secrete a vast array of cytokines, which influence both pro- anti-inflammatory responses. Indeed, similarly T cells, there is significant heterogeneity cytokine-driven by ranging from the production pro-inflammatory effector cytokines IL-6, through release immunosuppressive IL-10. In this review, focusing on human we summarize key findings have revealed cytokine-producing cell subsets critical functions healthy contribute pathophysiology autoimmune diseases.

Language: Английский

Citations

41