Chemokines are mainly studied for their local function in the control of leukocyte extravasation in homeostatic and inflammatory conditions. However, they have additional roles at the systemic level including the regulation of the hematopoietic process and leukocyte differentiation. Due to the redundancy and pleiotropicity of the chemokine system, chemokines have often multiple and complex roles in neutrophil differentiation ranging from retention and control of proliferation of progenitors to the mobilization of mature cells from the bone marrow (BM) to the bloodstream and their further differentiation in tissues. Atypical chemokine receptors (ACKRs) are regulators of the chemokine system by controlling chemokine bioavailability and chemokine receptor function. Even though ACKRs bind a wide range of chemokines, they appear to have a selective role in the process of neutrophil production and differentiation. The aim of this review is to give an overview of the current evidence regarding the role of chemokines and chemokine receptors in the life of neutrophils with a focus on the regulation exerted by ACKRs.
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http://dx.doi.org/10.1016/j.cyto.2023.156297 | DOI Listing |
EMBO J
January 2025
Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA.
The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Chimeric antigen receptor (CAR) T cell therapy for solid tumors faces significant challenges, including inadequate infiltration, limited proliferation, diminished effector function of CAR T cells, and an immunosuppressive tumor microenvironment (TME). In this study, we utilized The Cancer Genome Atlas database to identify key chemokines (CCL4, CCL5, and CCR5) associated with T cell infiltration across various solid tumor types. The CCL4/CCL5-CCR5 axis emerged as significantly correlated with the presence of T cells within tumors, and enhancing the expression of CCR5 in CAR T cells bolstered their migratory capacity.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Flanders Institute for Biotechnology, Antwerp, Belgium.
Background: Microglia are central players in Alzheimer's Disease (AD) pathology, but analyzing microglia states in human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies.
Method: To circumvent these issues, here we collected 138,577 single cell expression profiles of human stem cell derived-microglia from a xenotransplantation model of AD.
Result: Xenografted human microglia adopt a disease-associated (DAM) profile similar to that seen in mouse microglia, but display a more pronounced HLA state, likely related to antigen presentation in response to amyloid plaques.
Alzheimers Dement
December 2024
Medical University of South Carolina, Charleston, SC, USA.
Background: Specialized pro-resolving mediators (SPMs) promote inflammatory resolution and homeostasis and are thought to have specific reprogramming effects on hman microglia. Decreased SPM levels have been correlated with chronic neuroinflammation, late-stage Alzheimer's disease (AD) and neuropathology in humans, yet few studies have explored the cellular signatures of resolution. Amyloid is though to bind one target resolution receptor, ChemR23, leading to internalization.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Dysfunctional microglial activity has recently been identified as a potential mechanism leading to accumulation of amyloid beta and pTau and subsequent neurodegeneration in Alzheimer's Disease. The CX3CR1/fractalkine axis serves as a mechanism for bi-directional communication between microglia and neurons, respectively, to promote a resting, anti-inflammatory state in microglia. Previous studies have demonstrated that deficiency in CX3CR1 signaling leads microglia to a more pro-inflammatory phenotype, phagocytic deficits, and increased susceptibility of neurons to cell death.
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