Fc receptors (FcRs) are an important bridge between the innate and adaptive immune system. Fc gamma receptor I (FcγRI; CD64), the high-affinity receptor for immunoglobulin G (IgG), plays roles in inflammation, autoimmune responses, and immunotherapy. Stimulation of myeloid cells with cytokines, such as tumor necrosis factor-α ( TNFα) and interferon-γ ( IFNγ), increases the binding of FcγRI to immune complexes (ICs), such as antibody-opsonized pathogens or tumor cells, through a process known as "inside-out" signaling. Using super-resolution imaging, we found that stimulation of cells with IL-3 also enhanced the clustering of FcγRI both before and after exposure to ICs. This increased clustering was dependent on an intact actin cytoskeleton. We found that chemical inhibition of the activity of the phosphatase PP1 reduced FcγRI inside-out signaling, although the phosphorylation of FcγRI itself was unaffected. Furthermore, the antibody-dependent cytotoxic activity of human neutrophils toward CD20-expressing tumor cells was increased after stimulation with TNFα and IFNγ. These results suggest that nanoscale reorganization of FcγRI, stimulated by cytokine-induced, inside-out signaling, enhances FcγRI cellular effector functions.
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http://dx.doi.org/10.1126/scisignal.aaq0891 | DOI Listing |
Cell Commun Signal
January 2025
Department of Immunology, University of Connecticut School of Medicine, Connecticut, Farmington, 06030, USA.
Background: Neutrophils are the most abundant leukocytes in human blood, and their recruitment is essential for innate immunity and inflammatory responses. The initial and critical step of neutrophil recruitment is their adhesion to vascular endothelium, which depends on G protein-coupled receptor (GPCR) triggered integrin inside-out signaling that induces β2 integrin activation and clustering on neutrophils. Kindlin-3 and talin-1 are essential regulators for the inside-out signaling induced β2 integrin activation.
View Article and Find Full Text PDFNat Commun
January 2025
Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, P. R. China.
Delivering plasmid DNA (pDNA) to solid tumors remains a significant challenge due to the requirement for multiple transport steps and the need to promote delivery efficiency. Herein, we present a virus-mimicking hybrid lipoplex, composed of an arginine-rich cationic lipid, hyaluronic acid derivatives coated gold nanoparticles, and pDNA. This system induces cytoskeletal rearrangements through "outside-in" mechanical and "inside-out" biochemical signaling, overcoming intra- and intercellular barriers to enhance pDNA delivery.
View Article and Find Full Text PDFJ ISAKOS
December 2024
Twin Cities Orthopedics, Edina, MN, USA. Electronic address:
Medial meniscus ramp tears are tears of the posteromedial capsule or peripheral rim of the posteromedial meniscus that frequently occur with anterior cruciate ligament (ACL) tears. The incidence and prevalence of medial meniscus ramp tears has been increasing in the recent literature due to the increased understanding of the anatomy and diagnosis of these tears. When a patient presents with an ACL tear, a medial meniscus ramp tear should be suspected if the patient has a grade 3+ Lachman or pivot-shift exam, a vertical line of increased signal intensity in the posterior capsule or peripheral meniscus on magnetic resonance imaging (MRI), or posteromedial tibial plateau bone bruising on MRI.
View Article and Find Full Text PDFJ Gen Physiol
January 2025
Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, VA, USA.
Pannexin 1 (PANX1) is a member of a topologically related and stoichiometrically diverse family of large pore membrane ion channels that support the flux of signaling metabolites (e.g., ATP) and fluorescent dyes.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
December 2024
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114, Wroclaw, Poland.
Coelimycin (CPK) producer Streptomyces coelicolor A3(2) is a well-established model for the genetic studies of bacteria from the genus Streptomyces, renowned for their ability to produce a plethora of antibiotics and other secondary metabolites. Expression regulation of natural product biosynthetic gene clusters (BGCs) is highly complex, involving not only regulatory proteins, like transcription factors, but also the products of the biosynthetic pathway that may act as ligands for some regulators and modulate their activity. Here, we present the evidence that intracellular CPK precursor(s) (preCPK) is involved in a negative feedback loop repressing the CPK BGC.
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