scholarly journals CD209/CD14+ Dendritic Cells Characterization in Rheumatoid and Psoriatic Arthritis Patients: Activation, Synovial Infiltration, and Therapeutic Targeting

2022 ◽  
Vol 12 ◽  
Author(s):  
Viviana Marzaioli ◽  
Mary Canavan ◽  
Achilleas Floudas ◽  
Keelin Flynn ◽  
Ronan Mullan ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Expression Profiles ◽  
Receptor Expression ◽  
Inflammatory State ◽  
Healthy Control ◽  
Differential Increase ◽  
First Time ◽  
Stat Pathway

Dendritic cells (DC) have a key role in the initiation and progression of inflammatory arthritis (IA). In this study, we identified a DC population that derive from monocytes, characterized as CD209/CD14+ DC, expressing classical DC markers (HLADR, CD11c) and the Mo-DC marker (CD209), while also retaining the monocytic marker CD14. This CD209/CD14+ DC population is present in the circulation of Healthy Control (HC), with increased frequency in Rheumatoid Arthritis (RA) and Psoriatic arthritic (PsA) patients. We demonstrate, for the first time, that circulatory IA CD209/CD14+ DC express more cytokines (IL1β/IL6/IL12/TNFα) and display a unique chemokine receptor expression and co-expression profiles compared to HC. We demonstrated that CD209/CD14+ DC are enriched in the inflamed joint where they display a unique inflammatory and maturation phenotype, with increased CD40 and CD80 and co-expression of specific chemokine receptors, displaying unique patterns between PsA and RA. We developed a new protocol of magnetic isolation and expansion for CD209+ DC from blood and identified transcriptional differences involved in endocytosis/antigen presentation between RA and PsA CD209+ DC. In addition, we observed that culture of healthy CD209+ DC with IA synovial fluid (SF), but not Osteoarthritis (OA) SF, was sufficient to induce the development of CD209/CD14+ DC, leading to a poly-mature DC phenotype. In addition, differential effects were observed in terms of chemokine receptor and chemokine expression, with healthy CD209+ DC displaying increased expression/co-expression of CCR6, CCR7, CXCR3, CXCR4 and CXCR5 when cultured with RA SF, while an increase in the chemokines CCR3, CXCL10 and CXCL11 was observed when cultured with PsA SF. This effect may be mediated in part by the observed differential increase in chemokines expressed in RA vs PsA SF. Finally, we observed that the JAK/STAT pathway, but not the NF-κB pathway (driven by TNFα), regulated CD209/CD14+ DC function in terms of activation, inflammatory state, and migratory capacity. In conclusion, we identified a novel CD209/CD14+ DC population, which is active in the circulation of RA and PsA, an effect potentiated once they enter the joint. Furthermore, we demonstrated that JAK/STAT inhibition can be used as a therapeutic strategy to decrease the inflammatory state of the pathogenic CD209/CD14+ DC.

scholarly journals Rat Cytomegalovirus Virion-Associated Proteins R131 and R129 Are Necessary for Infection of Macrophages and Dendritic Cells

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 963
Author(s):  
Iris K. A. Jones ◽  
Nicole N. Haese ◽  
Philippe Gatault ◽  
Zachary J. Streblow ◽  
Takeshi F. Andoh ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Viral Entry ◽  
Chemokine Receptors ◽  
Bone Marrow Cells ◽  
Organ Transplant ◽  
Receptor Expression ◽  
In Vivo Model ◽  
Solid Organ

Cytomegalovirus (CMV) establishes persistent, latent infection in hosts, causing diseases in immunocompromised patients, transplant recipients, and neonates. CMV infection modifies the host chemokine axis by modulating chemokine and chemokine receptor expression and by encoding putative chemokine and chemokine receptor homologues. The viral proteins have roles in cellular signaling, migration, and transformation, as well as viral dissemination, tropism, latency and reactivation. Herein, we review the contribution of CMV-encoded chemokines and chemokine receptors to these processes, and further elucidate the viral tropism role of rat CMV (RCMV) R129 and R131. These homologues of the human CMV (HCMV)-encoded chemokines UL128 and UL130 are of particular interest because of their dual role as chemokines and members of the pentameric entry complex, which is required for entry into cell types that are essential for viral transmission and dissemination. The contributions of UL128 and UL130 to acceleration of solid organ transplant chronic rejection are poorly understood, and are in need of an effective in vivo model system to elucidate the phenomenon. We demonstrated similar molecular entry requirements for R129 and R131 in the rat cells, as observed for HCMV, and provided evidence that R129 and R131 are part of the viral entry complex required for entry into macrophages, dendritic cells, and bone marrow cells.

scholarly journals Leishmania major Modulates Chemokine and Chemokine Receptor Expression by Dendritic Cells and Affects Their Migratory Capacity

2005 ◽  
Vol 73 (4) ◽  
pp. 2564-2567 ◽  
Author(s):  
Mario Steigerwald ◽  
Heidrun Moll
Keyword(s):  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Leishmania Major ◽  
Chemotactic Response ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
Migratory Capacity

ABSTRACT Dendritic cells (DC) both produce and respond to chemokines. We examined the profiles of chemokines and chemokine receptors expressed by DC and their chemotactic response after interaction with Leishmania major. Expression of the chemokine receptors CCR2 and CCR5 by DC and their responsiveness to the respective ligands, CCL2 and CCL3, were downregulated, while the level of CCR7 and the DC response to its ligand CCL21 were enhanced. These parasite-induced alterations were observed with DC from L. major-resistant and -susceptible mice. In contrast, expression of the chemokine CXCL10 was elicited only in DC from L. major-resistant mice.

scholarly journals Biphasic Expression of Atypical Chemokine Receptor (ACKR) 2 and ACKR4 in Colorectal Neoplasms in Association with Histopathological Findings

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Paulina Lewandowska ◽  
Jaroslaw Wierzbicki ◽  
Marek Zawadzki ◽  
Anil Agrawal ◽  
Małgorzata Krzystek-Korpacka
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Chemokine Receptor ◽  
Growth Pattern ◽  
Chemokine Receptors ◽  
Receptor Expression ◽  
Transcriptional Analysis ◽  
Neoplastic Tissue ◽  
Node Metastasis ◽  
Affected Tissue

Facilitating resolution of inflammation using atypical chemokine receptors (ACKR) as an anticancer strategy is considered but requires a deeper understanding of receptor role in carcinogenesis. We aimed at transcriptional analysis (RTqPCR) of ACKR2 and ACKR4 expression in colorectal adenoma-adenocarcinoma sequence in paired normal-neoplastic tissues from 96 polyps and 51 cancers. On average, ACKR2 was downregulated in neoplastic as compared to non-affected tissue in polyp (by 2.7-fold) and cancer (by 3.1-fold) patients. The maximal downregulation (by 8.2-fold) was observed in adenomas with the highest potential for malignancy and was gradually lessening through cancer stages I-IV, owing to increased receptor expression in tumors. On average, ACKR4 was significantly downregulated solely in adenocarcinomas (by 1.5-fold), less so in patients with lymph node metastasis, owing to a gradual decrease in ACKR4 expression among N0-N1-N2 cancers in non-affected tissue without changes in tumors. In adenomas, ACKR4 downregulation in neoplastic tissue increased with increasing potential for malignancy and contribution of villous growth pattern. ACKR4 expression increased in non-affected tissue with a concomitant decrease in pathological mucosa. In conclusion, the changes in ACKRs expression occur already in precancerous colorectal lesions, culminating in the adenomas with the highest potential for malignancy. Therefore, chemoprevention by manipulating ACKRs’ expression is worth exploration.

scholarly journals Transcriptome of Hypoxic Immature Dendritic Cells: Modulation of Chemokine/Receptor Expression

2008 ◽  
Vol 6 (2) ◽  
pp. 175-185 ◽  
Author(s):  
Annamaria Ricciardi ◽  
Angela Rita Elia ◽  
Paola Cappello ◽  
Maura Puppo ◽  
Cristina Vanni ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Receptor Expression ◽  
Chemokine Receptor Expression ◽  
Immature Dendritic Cells

scholarly journals Human Immunodeficiency Virus-1 Entry Into Purified Blood Dendritic Cells Through CC and CXC Chemokine Coreceptors

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1379-1386 ◽  
Author(s):  
Seyoum Ayehunie ◽  
Eduardo A. Garcia-Zepeda ◽  
James A. Hoxie ◽  
Richard Horuk ◽  
Thomas S. Kupper ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Rna Transcripts ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
Cxc Chemokine ◽  
Cc Chemokines

Abstract Blood dendritic cells (DC) are susceptible to both macrophage (M) and T-cell line (T) tropic human immunodeficiency virus type 1. The CC chemokines RANTES, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, eotaxin, and, to a lesser extent, monocyte chemoattractant protein-1 (MCP-1) and MCP-4 blocked entry of M-tropic virus into blood DC. The CXC chemokine, SDF-1, a fusin (CXCR4 chemokine receptor) ligand, and an antifusin antibody inhibited DC entry by T-tropic virus. Purified blood DC contained CCR1, CCR2, CCR3, and CCR5 as well as the CXCR4 chemokine receptor RNA transcripts and high levels of fusin on the cell surface. The coexpression of multiple chemokine receptors offers a molecular mechanism to explain the permissiveness of DC for both M- and T-tropic viruses.

scholarly journals Chemokine and Chemokine Receptor Dynamics during Genital Chlamydial Infection

2002 ◽  
Vol 70 (2) ◽  
pp. 844-850 ◽  
Author(s):  
Tesfaye Belay ◽  
Francis O. Eko ◽  
Godwin A. Ananaba ◽  
Samera Bowers ◽  
Terri Moore ◽  
...  
Keyword(s):  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Primary Infection ◽  
Chlamydial Infection ◽  
Time Course ◽  
Secondary Infection ◽  
Receptor Expression ◽  
Microbial Pathogens ◽  
Intercellular Adhesion Molecule ◽  
Regulation Of Expression

ABSTRACT Current design strategies for vaccines against certain microbial pathogens, including Chlamydia trachomatis, require the induction and targeting of specific immune effectors to the local sites of infection known as the mucosal effector sites. Chemokines and their receptors are important mediators of leukocyte trafficking and of the controlled recruitment of specific leukocyte clonotypes during host defense against infections and during inflammation. We analyzed the dynamics of chemokine and chemokine receptor expression in genital mucosae during genital chlamydial infection in a murine model to determine how these molecular entities influence the development of immunity and the clearance of infection. A time course study revealed an increase of up to threefold in the levels of expression of RANTES, monocyte chemotactic protein 1 (MCP-1), gamma-interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1α (MIP-1α), and intercellular adhesion molecule type 1 (ICAM-1) after genital infection with the C. trachomatis agent of mouse pneumonitis. Peak levels of expression of RANTES, MCP-1, and MIP-1α occurred by day 7 after primary infection, while those of IP-10 and ICAM-1 peaked by day 21. Expression levels of these molecules decreased by day 42 after primary infection, by which time all animals had resolved the infection, suggesting an infection-driven regulation of expression. A rapid upregulation of expression of these molecules was observed after secondary infection. The presence of cells bearing the chemokine receptors CCR5 and CXCR3, known to be preferentially expressed on Th1 and dendritic cells, was also synchronous with the kinetics of immune induction in the genital tract and clearance of infection. Results demonstrated that genital chlamydial infection is associated with a significant induction of chemokines and chemokine receptors that are involved in the recruitment of Th1 cells into the site of infection. Future studies will focus on how selective modulation of chemokines and their receptors can be used to optimize long-term immunity against Chlamydia.

Neuropeptide substance P upregulates chemokine and chemokine receptor expression in primary mouse neutrophils

2007 ◽  
Vol 293 (2) ◽  
pp. C696-C704 ◽  
Author(s):  
Jia Sun ◽  
Raina Devi Ramnath ◽  
Madhav Bhatia
Keyword(s):  
Substance P ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Binding Activity ◽  
Receptor Expression ◽  
Chemokine Production ◽  
Chemokine Receptor Expression ◽  
Cc Chemokine ◽  
Primary Mouse ◽  
Cxc Chemokine

Neuropeptides play an important role in the active communication between the nervous and immune systems. Substance P (SP) is a prominent neuropeptide involved in neurogenic inflammation and has been reported to exert various proinflammatory actions on inflammatory leukocytes including neutrophils. The present study further investigated the modulatory effect of SP (1 μM) on chemokine production and chemokine receptor expression in primary mouse neutrophils. Our results showed that SP primed neutrophils for chemotactic responses not only to the CXC chemokine macrophage inflammatory protein (MIP)-2/CXCL2 but also to the CC chemokine MIP-1α/CCL3. The activating effect of SP on neutrophils was further evidenced by upregulation of the CD11b integrin, the activation marker of neutrophils. SP induced both the mRNA and protein expression of the chemokines MIP-1α/CCL3 and MIP-2/CXCL2 in neutrophils and upregulated the chemokine receptors CC chemokine receptor (CCR)-1 and CXC chemokine receptor (CXCR)-2. This stimulatory effect on chemokine and chemokine receptor expression in neutrophils was further found to be neurokinin-1 receptor (NK-1R) specific. Pretreatment with selective NK-1R antagonists inhibited SP-triggered activation of neutrophils and chemokine and chemokine receptor upregulation. Moreover, SP-induced chemokine upregulation was NF-κB dependent. SP time dependently induced NF-κB p65 binding activity, IκBα degradation, and NF-κB p65 nuclear translocation in neutrophils. Inhibition of NF-κB activation with its inhibitor Bay11-7082 (10 μM) abolished SP-induced NF-κB binding activity and upregulation of MIP-1α/CCL3 and MIP-2/CXCL2 in neutrophils. Together, these results suggest that SP exerts a direct stimulatory effect on the expression of chemokines and chemokine receptors in mouse neutrophils. The effect is NK-1R mediated, involving NF-κB activation.

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