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Università della Svizzera italiana

CXCR7 prevents excessive CXCL12-mediated downregulation of CXCR4 in migrating cortical interneurons

Abe, Philipp ; Mueller, Wiebke ; Schütz, Dagmar ; MacKay, Fabienne ; Thelen, Marcus ; Zhang, Penglie ; Stumm, Ralf

In: Development, 2014, vol. 141, no. 9, p. 1857-1863

The CXCL12/CXCR4 signaling pathway is involved in the development of numerous neuronal and non-neuronal structures. Recent work established that the atypical second CXCL12 receptor, CXCR7, is essential for the proper migration of interneuron precursors in the developing cerebral cortex. Two CXCR7-mediated functions were proposed in this process: direct modulation of β-arrestin-mediated...

Università della Svizzera italiana

Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus

Biajoux, Vincent ; Bignon, Alexandre ; Freitas, Christelle ; Martinez, Valérie ; Thelen, Marcus ; Lima, Guadalupe ; Jakez-Ocampo, Juan ; Emilie, Dominique ; Llorente, Luis ; Balabanian, Karl

In: Journal of translational medicine, 2012, vol. 10, no. 1, p. 251-267

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyperreactivity and the production of pathogenic anti-nuclear- directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among...

Università della Svizzera italiana

Cxcl12 evolution – subfunctionalization of a ligand through altered interaction with the chemokine receptor

Boldajipour, Bijan ; Doitsidou, Maria ; Tarbashevich, Katsiaryna ; Laguri, Cedric ; Yu, Shuizi Rachel ; Ries, Jonas ; Dumstrei, Karin ; Thelen, Sylvia ; Dörries, Julia ; Messerschmidt, Esther-Maria ; Thelen, Marcus ; Schwille, Petra ; Brand, Michael ; Lortat-Jacob, Hugues ; Raz, Erez

In: Development, 2011, vol. 138, no. 14, p. 2909-2914

The active migration of primordial germ cells (PGCs) from their site of specification towards their target is a valuable model for investigating directed cell migration within the complex environment of the developing embryo. In several vertebrates, PGC migration is guided by Cxcl12, a member of the chemokine superfamily. Interestingly, two distinct Cxcl12 paralogs are expressed in zebrafish...

Università della Svizzera italiana

Expression of the chemokine receptor CXCR7 in CXCR4-expressing human 143B osteosarcoma cells enhances lung metastasis of intratibial xenografts in SCID mice

Brennecke, Patrick ; Arlt, Matthias J. E. ; Muff, Roman ; Campanile, Carmen ; Gvozdenovic, Ana ; Husmann, Knut ; Holzwarth, Nathalie ; Cameroni, Elisabetta ; Ehrensperger, Felix ; Thelen, Marcus ; Born, Walter ; Fuchs, Bruno

In: Plos one, 2013, vol. 8, no. 9, p. e74045

More effective treatment of metastasizing osteosarcoma with a current mean 5-year survival rate of less than 20% requires more detailed knowledge on mechanisms and key regulatory molecules of the complex metastatic process. CXCR4, the receptor of the chemokine CXCL12, has been reported to promote tumor progression and metastasis in osteosarcoma. CXCR7 is a recently deorphanized...

Università della Svizzera italiana

Herpes simplex virus enhances chemokine function through modulation of receptor trafficking and oligomerization

Martinez-Martin, Nadia ; Viejo-Borbolla, Abel ; Martín, Rocío ; Soledad, Blanco ; Benovic, Jeffrey L. ; Thelen, Marcus ; Alcamí, Antonio

In: Nature communications, 2015, vol. 6, p. 6163

Glycoprotein G (gG) from herpes simplex virus 1 and 2 (HSV-1 and HSV-2, important human neurotropic pathogens) is the first viral chemokine-binding protein found to potentiate chemokine function. Here we show that gG attaches to cell surface glycosaminoglycans and induces lipid raft clustering, increasing the incorporation of CXCR4 receptors into these microdomains. gG induces conformational...

Università della Svizzera italiana

The atypical receptor CCRL2 (C-C Chemokine Receptor-Like 2) does not act as a decoy receptor in endothelial cells

Mazzotti, Chiara ; Gagliostro, Vincenzo ; Bosisio, Daniela ; Del Prete, Annalisa ; Tiberio, Laura ; Thelen, Marcus ; Sozzani, Silvano

In: Frontiers in immunology, 2017, vol. 8, p. 1233

C-C chemokine receptor-like 2 (CCRL2) is a non-signaling seven-transmembrane domain (7-TMD) receptor related to the atypical chemokine receptor (ACKR) family. ACKRs bind chemokines but do not activate G protein-dependent signaling or cell functions. ACKRs were shown to regulate immune functions in vivo by their ability to scavenge chemokines from the local environment. This study was ...

Università della Svizzera italiana

CXCR7 functions as a scavenger for CXCL12 and CXCL11

Naumann, Ulrike ; Cameroni, Elisabetta ; Pruenster, Monika ; Mahabaleshwar, Harsha ; Raz, Erez ; Zerwes, Hans-Günter ; Rot, Antal ; Thelen, Marcus

In: Plos one, 2010, vol. 5, no. 2, p. e9175

Background: CXCR7 (RDC1), the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses. The function of CXCR7 is controversial. Some studies suggest a signaling activity in mammalian cells and zebrafish embryos, while others indicate a decoy...

Università della Svizzera italiana

ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens

Proietti, Michele ; Perruzza, Lisa ; Scribano, Daniela ; Pellegrini, Giovanni ; D’Antuono, Rocco ; Strati, Francesco ; Raffaelli, Marco ; Gonzalez, Santiago F. ; Thelen, Marcus ; Hardt, Wolf-Dietrich ; Slack, Emma ; Nicoletti, Mauro ; Grassi, Fabio

In: Nature Communications, 2019, vol. 10, p. Art. number: 250

T cell dependent secretory IgA (SIgA) generated in the Peyer’s patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host’s immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells...

Università della Svizzera italiana

ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration

Puddinu, Viola ; Casella, Sabrina ; Radice, Egle ; Thelen, Sylvia ; Dirnhofer, Stefan ; Bertoni, Francesco ; Thelen, Marcus

In: Oncotarget, 2017, vol. 8, no. 49, p. 85068-85084

Diffuse large B cell lymphoma (DLBCL) is the most frequent lymphoma accounting for more than the 30% of the cases. Involvement of extranodal sites, such as bone marrow and central nervous system, is associated with poor prognosis. A contribution of the chemokine system in these processes is assumed as it is known as a critical regulator of the metastatic process in cancer. The atypical...

Università della Svizzera italiana

HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4

Schiraldi, Milena ; Raucci, Angela ; Martínez Muñoz, Laura ; Livoti, Elsa ; Celona, Barbara ; Venereau, Emilie ; Apuzzo, Tiziana ; De Marchis, Francesco ; Pedotti, Mattia ; Bachi, Angela ; Thelen, Marcus ; Varani, Luca ; Mellado, Mario ; Proudfoot, Amanda ; Bianchi, Marco Emilio ; Uguccioni, Mariagrazia

In: The journal of experimental medicine, 2012, vol. 209, no. 3, p. 551-563

After tissue damage, inflammatory cells infiltrate the tissue and release proinflammatory cytokines. HMGB1 (high mobility group box 1), a nuclear protein released by necrotic and severely stressed cells, promotes cytokine release via its interaction with the TLR4 (Toll-like receptor 4) receptor and cell migration via an unknown mechanism. We show that HMGB1- induced recruitment of inflammatory...