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Università della Svizzera italiana

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Jacquelot, Nicolas ; Enot, David P. ; Flament, Caroline ; Vimond, Nadège ; Blattner, Carolin ; Pitt, Jonathan M. ; Yamazaki, Takahiro ; Roberti, María Paula ; Daillère, Romain ; Vétizou, Marie ; Poirier-Colame, Vichnou ; Semeraro, Michaëla ; Caignard, Anne ; Slingluff Jr., Craig L. ; Sallusto, Federica ; Rusakiewicz, Sylvie ; Weide, Benjamin ; Marabelle, Aurélien ; Kohrt, Holbrook ; Dalle, Stéphane ; Cavalcanti, Andréa ; Kroemer, Guido ; Di Giacomo, Anna Maria ; Maio, Michele ; Wong, Phillip ; Yuan, Jianda ; Wolchok, Jedd ; Umansky, Viktor ; Eggermont, Alexander ; Zitvogel, Laurence

In: The journal of clinical investigation, 2016, vol. 126, no. 3, p. 921-937

Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate...

Università della Svizzera italiana

Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects

Rigoni, Rosita ; Fontana, Elena ; Guglielmetti, Simone ; Fosso, Bruno ; D’Erchia, Anna Maria ; Maina, Virginia ; Taverniti, Valentina ; Carmina Castiello, Maria ; Mantero, Stefano ; Pacchiana, Giovanni ; Musio, Silvia ; Pedotti, Rosetta ; Selmi, Carlo ; Mora, J. Rodrigo ; Pesole, Graziano ; Vezzoni, Paolo ; Poliani, Pietro Luigi ; Grassi, Fabio ; Villa, Anna ; Cassani, Barbara

In: The journal of experimental medicine, 2016, vol. 213, no. 3, p. 355-375

Omenn syndrome (OS) is caused by hypomorphic Rag mutations and characterized by a profound immunodeficiency associated with autoimmune-like manifestations. Both in humans and mice, OS is mediated by oligoclonal activated T and B cells. The role of microbial signals in disease pathogenesis is debated. Here, we show that Rag2R229Q knock-in mice developed an inflammatory bowel disease affecting...

Università della Svizzera italiana

Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

Venereau, Emilie ; Casalgrandi, Maura ; Schiraldi, Milena ; Antoine, Daniel J. ; Cattaneo, Angela ; De Marchis, Francesco ; Liu, Jaron ; Antonelli, Antonella ; Preti, Alessandro ; Raeli, Lorenzo ; Samadi Shams, Sara ; Yang, Huan ; Varani, Luca ; Andersson, Ulf ; Tracey, Kevin J. ; Bachi, Angela ; Uguccioni, Mariagrazia ; Bianchi, Marco E.

In: The journal of experimental medicine, 2012, vol. 209, no. 9, p. 1519-1528

Tissue damage causes inflammation, by recruiting leukocytes and activating them to release proinflammatory mediators. We show that high-mobility group box 1 protein (HMGB1) orchestrates both processes by switching among mutually exclusive redox states. Reduced cysteines make HMGB1 a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine and further cysteine oxidation to...

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

Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition

Amara, Khaled ; Steen, Johanna ; Murray, Fiona ; Morbach, Henner ; Fernandez-Rodriguez, Blanca M. ; Joshua, Vijay ; Engström, Marianne ; Snir, Omri ; Israelsson, Lena ; Catrina, Anca I. ; Wardemann, Hedda ; Corti, Davide ; Meffre, Eric ; Klareskog, Lars ; Malmström, Vivianne

In: The journal of experimental medicine, 2013, vol. 210, no. 3, p. 445-455

Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class...

Università della Svizzera italiana

miR-146a and NF-κB1 regulate mast cell survival and T lymphocyte differentiation

Rusca, Nicole ; Dehò, Lorenzo ; Montagner, Sara ; Zielinski, Christina E. ; Sica, Antonio ; Sallusto, Federica ; Monticelli, Silvia

In: Molecular and cellular biology, 2012, vol. 32, no. 21, p. 4432-4444

The transcription factor NF-κB regulates the expression of a broad number of genes central to immune and inflammatory responses. We identified a new molecular network that comprises specifically the NF-κB family member NF-κB1 (p50) and miR-146a, and we show that in mast cells it contributes to the regulation of cell homeostasis and survival, while in T lymphocytes it modulates T cell...

Università della Svizzera italiana

Antibody binding modulates conformational exchange in domain III of dengue virus E protein

Moraes, Adolfo H. ; Simonelli, Luca ; Pedotti, Mattia ; Almeida, Fabio C.L. ; Varani, Luca ; Valente, Ana P.

In: Journal of virology, 2016, vol. 90, no. 4, p. 1802-1811

Domain III of dengue virus E protein (DIII) participates in the recognition of cell receptors and in structural rearrangements required for membrane fusion and ultimately viral infection; furthermore, it contains epitopes for neutralizing antibodies and has been considered a potential vaccination agent. In this work, we addressed various structural aspects of DIII and their relevance for both...

Università della Svizzera italiana

The protein disulfide isomerase ERp57 regulates the steady-state levels of the prion protein

Torres, Mauricio ; Medinas,Danilo B. ; Matamala, José Manuel ; Woehlbier, Ute ; Cornejo, Víctor Hugo ; Solda, Tatiana ; Andreu, Catherine ; Rozas, Pablo ; Matus, Soledad ; Muñoz, Natalia ; Vergara, Carmen ; Cartier, Luis ; Soto, Claudio ; Molinari, Maurizio ; Hetz, Claudio

In: The journal of biological chemistry, 2015, vol. 290, no. 39, p. 23631-23645

Although the accumulation of a misfolded and protease-resistant form of the prion protein (PrP) is a key event in Prion pathogenesis, the cellular factors involved in its folding and quality control are poorly understood. PrP is a glycosylated and disulfide-bonded protein synthesized at the endoplasmic reticulum (ER). The ER foldase ERp57 (also known as Grp58) is highly expressed in the brain...

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

Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies

Kabanovaa, Anna ; Perez, Laurent ; Lilleri, Daniele ; Marcandalli, Jessica ; Agatic, Gloria ; Becattini, Simone ; Preite, Silvia ; Fuschillo, Dario ; Percivalle,Elena ; Sallusto, Federica ; Gerna, Giuseppe ; Corti, Davide ; Lanzavecchia, Antonio

In: Proceedings of the national academy of sciences of the United States of America, 2014, vol. 111, no. 50, p. 17965-17970

The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV...