Abstract The CCL2 chemokine mediates monocyte egress from bone marrow and recruitment into inflamed tissues through interaction with the CCR2 receptor, its expression is upregulated by proinflammatory cytokines. Analysis of gene profile in GM-CSF– M-CSF–polarized macrophages revealed that a high characterizes generated under influence M-CSF, whereas expressed only GM-CSF–polarized macrophages. factors responsible for this differential identified activin A as critical factor controlling...

Macrophage activation comprises a continuum of functional states critically determined by cytokine microenvironment. Activated macrophages have been functionally grouped according to their response pro-Th1/proinflammatory stimuli [lipopolysaccharide, IFNgamma, granulocyte macrophage colony-stimulating factor (GM-CSF); M1] or pro-Th2/anti-inflammatory [interleukin (IL)-4, IL-10, M-CSF; M2]. We report that folate receptor beta (FRbeta), encoded the FOLR2 gene, is marker for generated in...

Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) is a monocyte-derived dendritic cell (MDDC)-specific lectin which participates in (DC) migration and DC-T lymphocyte interactions at the initiation of immune responses enhances trans-infection T cells through its HIV gp120-binding ability. The generation DC-SIGN-specific mAb has allowed us to determine that acquisition DC-SIGN expression during monocyte-DC differentiation pathway primarily induced by IL-4, GM-CSF cooperates with...

Besides its role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5HT) regulates inflammation and tissue repair via set of receptors (5HT(1-7)) whose pattern expression varies among cell lineages. Considering the importance macrophage polarization plasticity for inflammatory responses repair, we evaluated whether 5HT modulates human polarization. inhibited LPS-induced release proinflammatory cytokines without affecting IL-10 production, upregulated M2 polarization-associated genes...

The shift between pro-inflammatory (M1) and anti-inflammatory (M2) states of macrophage polarization allows the resolution inflammatory processes as well maintenance a basal environment in tissues continuously exposed to harmless antigens (e.g., lung gut). To identify markers for state macrophages, expression profiling was performed on human macrophages polarized by either GM-CSF or M-CSF, which lead generation TNF-alpha IL-12p40-producing [M1 (GM-CSF)] IL-10-producing [M2 (M-CSF)] upon...

Abstract Rheumatoid arthritis ( RA ) is a chronic inflammatory disease whose pathogenesis and severity correlates with the presence of macrophage‐derived pro‐inflammatory cytokines within inflamed synovium. Macrophage‐derived fuel pathological processes in are targets clinically successful therapies. However, although macrophage polarization determines cytokine production, state macrophages joints remains poorly defined. To dissect molecular basis for tissue‐damaging effects joints, we...

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN; CD209) is a human pathogen-attachment C-type lectin with no obvious murine ortholog and for which ligation leads to enhanced anti-inflammatory cytokine release altered proinflammatory production. Although induced by IL-4 in monocytes considered as DC marker, DC-SIGN expression on APCs under homeostatic conditions so far unexplained. We report this study that M-CSF enhances vitro derived macrophages mediates the induction of...

Dendritic cells (DCs) play a critical role in the initiation of immunological response against Leishmania parasites. However, receptors involved amastigote-dendritic cell interaction are unknown, especially absence opsonizing antibodies. We have studied pifanoi axenic amastigotes with C-type lectin DC-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN, CD209), receptor for ICAM-2, ICAM-3, human immunodeficiency virus gp120, and Ebola virus. L. interact immature...

Tumour cell dissemination through corporal fluids (blood, lymph and body cavity fluids) is a distinctive feature of the metastatic process. transition from fluid to adhesive conditions involves an early polarization event major rearrangements submembrane cytoskeleton that remain poorly understood. As regulation cortical actin-membrane binding might be important in this process, we investigated role ezrin moesin, which are key crosslinking proteins ERM (ezrin, radixin, moesin) family. We used...

Abstract Introduction Circulating CD4 T cells expressing CXCR5, ICOS and/or PD-1 are counterparts of follicular helper (Tfh). There three subpopulations circulating Tfh (cTfh): CXCR5 + CXCR3 CCR6- (Tfh-Th1), CXCR3-CCR6- (Tfh-Th2) and CXCR3-CCR6+ (Tfh-Th17). Our objective was to study the B cell helping capacity cTfh subsets, examine their frequency in Rheumatoid Arthritis (RA) patients, together with plasmablasts (CD19 CD20-CD38 high ). Methods Peripheral blood drawn from RA patients active...

Abstract Objective A novel population of B helper cells, phenotypically CD4+CXCR5−PD-1hi, has been described in the synovial tissues and peripheral blood seropositive RA patients, termed ‘peripheral T’ (Tph) cells. Contrary to CD4+CXCR5+PD-1hi follicular T (Tfh), Tph cells are not located lymphoid organs but accumulate inflamed tissues. Our objective was study frequency circulating (cTph) Tfh cell counterparts (cTfh) patients with early (eRA). Methods Freshly isolated mononuclear from 56...

Distinct subsets of dendritic cells (DCs) are present in blood, probably "en route" to different tissues. We have investigated the chemokines and adhesion molecules involved migration myeloid (CD11c(+)) plasmacytoid (CD123(+)) human peripheral blood DCs across vascular endothelium. Among DCs, CD11c(+) subset vigorously migrated endothelium absence any chemotactic stimuli, whereas spontaneous CD123(+) was limited. In bare cell assays, responded with great potency several inflammatory...

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and mediates binding internalization of pathogens such virus (human immunodeficiency virus, hepatitis C), bacteria (Mycobacterium), fungi, parasites. DC-SIGN expression in vivo primarily restricted to interstitial dendritic cells (DC) certain tissue macrophages. We now report leukemic THP-1 cells, widely used model for monocyte-macrophage differentiation, express...

ABSTRACT Vitamin B9, commonly known as folate, is an essential cofactor for one-carbon metabolism that enters cells through three major specialized transporter molecules (RFC, FR, and PCFT), which differ in expression pattern, affinity substrate, ligand-binding pH dependency. We now report the of folate transporters differs between macrophage subtypes explains higher accumulation 5-MTHF—the form found serum—in M2 macrophages vitro vivo. M1 display a RFC, whereas FRβ PCFT are preferentially...

Background and Aims GM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated (UA) by analyzing GM-CSF expression source, density joints of patients with UA evolving RA or PsA compared established PsA, respectively. Methods Synovial tissue (ST) from (UA>RA, n=8), (UA>PsA, n=9), persistent (UA, n=16), (n=12) (n=10), healthy controls (n=6), were analyzed. Cell source...

Abstract Monocyte-derived macrophages contribute to pathogenesis in inflammatory diseases and their effector functions greatly depend on the prevailing extracellular milieu. Whereas M-CSF primes for acquisition of an anti-inflammatory profile, GM-CSF drives generation T cell-stimulatory pro-inflammatory macrophages. Liver X Receptors (LXRα LXRβ) are nuclear receptors that control cholesterol metabolism regulate differentiation tissue-resident Macrophages from rheumatoid arthritis other...

Abstract Monocyte-derived macrophages play a key pathogenic role in inflammatory diseases. In the case of rheumatoid arthritis (RA), presence specific synovial tissue-infiltrating macrophage subsets is associated with either active disease or inflammation resolution. JAK inhibitors (JAKi) are first targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) approved for treatment RA comparable efficacy to biologics. However, effects JAKi on specification and differentiation currently...

Monocyte-derived macrophages recruited into inflamed tissues can acquire an array of functional states depending on the extracellular environment. Since anti-inflammatory/pro-fibrotic macrophage profile is determined by MAFB, whose activity/protein levels are regulated GSK3, we addressed re-programming potential GSK3 modulation. GM-CSF-dependent (GM-MØ) and M-CSF-dependent monocyte-derived (M-MØ) exhibited distinct inactive inhibiting in GM-MØ led to acquisition transcriptional, phenotypic...

Monocyte-derived macrophages recruited into inflamed tissues can acquire an array of functional states depending on the extracellular environment. Since anti-inflammatory/pro-fibrotic macrophage profile is determined by MAFB, whose activity/protein levels are regulated GSK3, we addressed re-programming potential GSK3 modulation. GM-CSF-dependent (GM-MØ) and M-CSF-dependent monocyte-derived (M-MØ) exhibited distinct inactive inhibiting in GM-MØ led to acquisition transcriptional, phenotypic...

Abstract Dendritic cells (DC) are highly specialized APC that critical for the initiation of T cell-dependent immune responses. DC exert a sentinel function while immature and, after activation by inflammatory stimuli or infectious agents, mature and migrate into lymphoid organs to prime cells. We have analyzed integrin expression on monocyte-derived (MDDC) found CD49d integrins (CD49d/CD29 CD49d/β7) was induced/up-regulated during TNF-α- LPS-initiated MDDC maturation, reflecting...

To examine the frequency and phenotype of Th17 cells in peripheral blood early RA (eRA) patients.CD4+ T were isolated from 33 eRA patients, 20 established patients 53 healthy controls (HC), synovial fluid (RASF), by ficoll-hypaque gradient magnetical negative selection. After polyclonal stimulation, Th1 was determined flow cytometry concentrations IL-17, IFN-γ, TNF-α IL-10 measured ELISA cell-free supernatants.When all our analyzed together, a significantly lower percentage circulating...