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

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

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...

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...