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Università della Svizzera italiana

Phenotype and specificity of T cells in primary human cytomegalovirus infection during pregnancy : IL-7Rpos long-term memory phenotype is associated with protection from vertical transmission

Mele, Federico ; Fornara, Chiara ; Jarrossay, David ; Furione, Milena ; Arossa, Alessia ; Spinillo, Arsenio ; Lanzavecchia, Antonio ; Gerna, Giuseppe ; Sallusto, Federica ; Lilleri, Daniele

In: Plos one, 2017, vol. 12, no. 11, p. e0187731

Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve...

Università della Svizzera italiana

Molecular signatures of immunity and immunogenicity in infection and vaccination

Haks, Mariëlle C. ; Bottazzi, Barbara ; Cecchinato, Valentina ; De Gregorio, Corinne ; Del Giudice, Giuseppe ; Kaufmann, Stefan H. E. ; Lanzavecchia, Antonio ; Lewis, David J. M. ; Maertzdorf, Jeroen ; Mantovani, Alberto ; Sallusto, Federica ; Sironi, Marina ; Uguccioni, Mariagrazia ; Ottenhoff, Tom H. M.

In: Frontiers in immunology, 2017, vol. 8, p. 1563

Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable...

Università della Svizzera italiana

Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis

Hu, Dan ; Notarbartolo, Samuele ; Croonenborghs, Tom ; Patel, Bonny ; Cialic, Ron ; Yang, Tun-Hsiang ; Aschenbrenner, Dominik ; Andersson, Karin M. ; Gattorno, Marco ; Pham, Minh ; Kivisakk, Pia ; Pierre, Isabelle V. ; Lee, Youjin ; Kiani, Karun ; Bokarewa, Maria ; Tjon, Emily ; Pochet, Nathalie ; Sallusto, Federica ; Kuchroo, Vijay K. ; Weiner, Howard L.

In: Nature communications, 2017, vol. 8, p. 1600

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ−IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene...

Università della Svizzera italiana

Epigenetic and transcriptional control of mast cell responses

Monticelli, Silvia ; Leoni

In: F1000 research, 2017, vol. 6, p. 2064

Mast cells are tissue-resident, innate immune cells present in most tissues of the body and are important effector and immunomodulatory cells. Differentiated mast cells typically are characterized by the surface expression of the receptors KIT and FcεRI, the latter especially being important for stimulation through IgE antibodies, although these cells have the ability to respond to a wide...

Università della Svizzera italiana

TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut

Romagnani, Andrea ; Vettore, Valentina ; Rezzonico-Jost, Tanja ; Hampe, Sarah ; Rottoli, Elsa ; Nadolni, Wiebke ; Perotti, Michela ; Meier, Melanie A. ; Hermanns, Constanze ; Geiger, Sheila ; Wennemuth, Gunther ; Recordati, Camilla ; Matsushita, Masayuki ; Muehlich, Susanne ; Proietti, Michele ; Chubanov, Vladimir ; Gudermann, Thomas ; Grassi, Fabio ; Zierler, Susanna

In: Nature communications, 2017, vol. 8, p. 1917

The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of ...

Università della Svizzera italiana

Dissecting human antibody responses: useful, basic and surprising findings

Lanzavecchia, Antonio

In: EMBO molecular medicine, 2018, vol. 10, p. e8879

Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells...

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

SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination

Daddacha, Waaqo ; Koyen, Allyson E. ; Bastien, Amanda J. ; Head,Pamela Sara E. ; Dhere, Vishal R. ; Nabeta, Geraldine N. ; Connolly, Erin C. ; Werner, Erica ; Madden, Matthew Z. ; Daly, Michele B. ; Minten, Elizabeth V. ; Whelan, Donna R. ; Schlafstein, Ashley J. ; Zhang, Hui ; Anand, Roopesh ; Doronio, Christine ; Withers, Allison E. ; Shepard, Caitlin ; Sundaram, Ranjini K. ; Deng, Xingming ; Dynan, William S. ; Wang, Ya ; Bindra, Ranjit S. ; Cejka, Petr ; Rothenberg, Eli ; Doetsch, Paul W. ; Kim, Baek ; Yu, David S.

In: Cell reports, 2017, vol. 20, no. 8, p. 1921-1935

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV- 1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate...

Università della Svizzera italiana

CXCL12α/SDF‐1 from perisynaptic Schwann cells promotes regeneration of injured motor axon terminals

Negro, Samuele ; Lessi, Francesca ; Duregotti, Elisa ; Aretini, Paolo ; La Ferla, Marco ; Franceschi, Sara ; Menicagli, Marco ; Bergamin, Elisanna ; Egle, Radice ; Megighian, Aram ; Pirazzini, Marco ; Mazzanti, Chiara M. ; Rigoni, Michela ; Montecucco, Cesare

In: EMBO molecular medicine, 2017, vol. 9, no. 8, p. 1000–1010

The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter‐cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal‐derived factor‐1 (SDF‐1), is produced specifically by perisynaptic Schwann cells following ...

Università della Svizzera italiana

T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP

Perruzza, Lisa ; Gargari, Giorgio ; Proietti, Michele ; Fosso, Bruno ; D'Erchia, Anna Maria ; Faliti, Caterina Elisa ; Rezzonico-Jost, Tanja ; Scribano, Daniela ; Mauri, Laura ; Colombo, Diego ; Pellegrini, Giovanni ; Moregola, Annalisa ; Mooser, Catherine ; Pesole, Graziano ; Nicoletti, Mauro ; Norata, Giuseppe Danilo ; Geuking, Markus B. ; McCoy, Kathy D. ; Guglielmetti, Simone ; Grassi, Fabio

In: Cell reports, 2017, vol. 18, no. 11, p. 2566-2575

The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer’s patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of...