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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...

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

Chemokines : chemistry, biochemistry and biological function

Legler, Daniel F. ; Thelen, Marcus

In: Chimia : International journal for chemistry, 2016, vol. 70, no. 12, p. 856-859

The in vitro synthesis of correctly folded functional proteins remains challenging. Chemokines, which consist of only 70–100 amino acids, are accessible through solid- phase synthesis and easily fold into a thermally stable tertiary structure. From the time of their discovery in the late 1980s chemokines could therefore be synthesized using biochemical and chemical protocols for...

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

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

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...