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Università della Svizzera italiana

New insights in chemokine signaling

Legler, Daniel F. ; Thelen, Marcus

In: F1000Research, 2018, vol. 7, p. 95

Chemokine signaling is essential for coordinated cell migration in health and disease to specifically govern cell positioning in space and time. Typically, chemokines signal through heptahelical, G protein-coupled receptors to orchestrate cell migration. Notably, chemokine receptors are highly dynamic structures and signaling efficiency largely depends on the discrete contact with the ligand....

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

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

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

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Zohar, Yaniv ; Wildbaum, Gizi ; Novak, Rostislav ; Salzman, Andrew L. ; Thelen, Marcus ; Alon, Ronen ; Barsheshet, Yiftah ; Karp, Christopher L. ; Karin, Nathan

In: The journal of clinical investigation, 2014, vol. 124, no. 5, p. 2009-2022

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown...

Università della Svizzera italiana

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

Zohar, Yaniv ; Wildbaum, Gizi ; Novak, Rostislav ; Salzman, Andrew L. ; Thelen, Marcus ; Alon, Ronen ; Barsheshet, Yiftah ; Karp, Christopher L. ; Karin, Nathan

In: The journal of clinical investigation, 2018, vol. 128, no. 3, p. 1200-1201

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown...

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

CCR2 acts as scavenger for CCL2 during monocyte chemotaxis

Volpe, Silvia ; Cameroni, Elisabetta ; Moepps, Barbara ; Thelen, Sylvia ; Apuzzo, Tiziana ; Thelen, Marcus

In: Plos one, 2012, vol. 7, no. 5, p. e37208

Background: Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces...

Università della Svizzera italiana

Enhancement of chemokine function as an immunomodulatory strategy employed by human herpesviruses

Viejo-Borbolla, Abel ; Martinez-Martín, Nadia ; Nel, Hendrik J. ; Rueda, Patricia ; Martín, Rocío ; Blanco, Soledad ; Arenzana-Seisdedos, Fernando ; Thelen, Marcus ; Fallon, Padraic G. ; Alcamí, Antonio

In: Plos pathogens, 2012, vol. 8, no. 2, p. e1002497

Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is...

Università della Svizzera italiana

Redox-mediated mechanisms fuel monocyte responses to CXCL12/HMGB1 in active rheumatoid arthritis

Cecchinato, Valentina ; D'Agostino, Gianluca ; Raeli, Lorenzo ; Nerviani, Alessandra ; Schiraldi, Milena ; Danelon, Gabriela ; Manzo, Antonio ; Thelen, Marcus ; Ciurea, Adrian ; Bianchi, Marco E. ; Rubartelli, Anna ; Pitzalis, Costantino ; Uguccioni, Mariagrazia

In: Frontiers in immunology, 2018, vol. 9, p. 2118

Chemokine synergy-inducing molecules are emerging as regulating factors in cell migration. The alarmin HMGB1, in its reduced form, can complex with CXCL12 enhancing its activity on monocytes via the chemokine receptor CXCR4, while the form containing a disulfide bond, by binding to TLR2 or TLR4, initiates a cascade of events leading to production of cytokines and chemokines. So far, the...