{"id":22328,"date":"2019-07-12T14:21:31","date_gmt":"2019-07-12T12:21:31","guid":{"rendered":"https:\/\/irb.usi.ch\/?page_id=22328"},"modified":"2026-01-15T11:06:33","modified_gmt":"2026-01-15T09:06:33","slug":"chemochine-ed-immunita","status":"publish","type":"page","link":"https:\/\/irb.usi.ch\/it\/chemochine-ed-immunita\/","title":{"rendered":"Chemochine ed immunit\u00e0"},"content":{"rendered":"\t\t
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Chemokine ed Immunit\u00e0<\/p>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Panoramica<\/p>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Il nostro interesse di ricerca rimane focalizzato sul traffico cellulare nella fisiologia e patologia umana, con particolare attenzione ai meccanismi che regolano la modulazione dell\u2019espressione e dell\u2019attivit\u00e0 delle chemochine, molecole chiave nel controllo della migrazione cellulare, e dei loro recettori. Gli effetti delle chemochine sono mediati da recettori a sette domini transmembrana che sono differenzialmente espressi in una vasta gamma di cellule del sangue e non solo. La diversit\u00e0 di espressione dei recettori e la loro reattivit\u00e0 alle chemochine garantiscono la corretta distribuzione tissutale dei diversi tipi di globuli bianchi sia in condizioni normali che patologiche.<\/p>

Il nostro gruppo ha descritto un meccanismo di regolazione della migrazione leucocitaria che mostra come diverse molecole possano indurre i globuli bianchi a rispondere a concentrazioni di chemochine che per s\u00e9 sarebbero inattive, abbassando cos\u00ec la loro \u201csoglia migratoria\u201d. Ad oggi ci sono ancora vari aspetti di questo effetto che chiamiamo \u201csinergia\u201d che dobbiamo chiarire, in vista di avere terapie pi\u00f9 efficaci per promuovere la risoluzione dell\u2019infiammazione, sia nelle patologie acute che in quelle croniche, come ad esempio nelle malattie autoimmuni. Durante infezioni virali, come ad esempio nell\u2019AIDS, la risposta delle cellule del sistema immunitario a stimoli importanti per il loro reclutamento negli organi da proteggere viene alterata. Un recente studio su individui guariti da COVID-19, svolto in collaborazione con i gruppi di Davide Robbiani e Andrea Cavalli, ha portato alla scoperta di autoanticorpi anti-chemochine che vengono generati durante l\u2019infezione e si mantengono per un lungo periodo, associandosi a protezione da sintomi legati al Long Covid. I nostri studi sul traffico leucocitario nell\u2019uomo, hanno portato nel corso del 2024 ad identificare, nei pazienti con Spondilite Anchilosante, una popolazione di linfociti T che si caratterizzano per l\u2019espressione di geni che promuovono l\u2019ossificazione e che potrebbero rappresentare un nuovo target terapeutico per migliorare la terapia di questa patologia. Sempre nel 2024 abbiamo esteso la nostra ricerca sullo studio delle interazioni tra allarmine e chemochine nei tumori, ed in particolare evidenziato quanto questo meccanismo possa essere importante nello sviluppo di metastasi.<\/p>

Queste scoperte aprono la strada all\u2019identificazione di nuovi target terapeutici in pazienti con infezioni acute o persistenti, malattie infiammatorie croniche e tumori, favorendo il ripristino delle funzioni di popolazioni cellulari attive nella risposta immunitaria o inibendo l\u2019eccessiva funzione delle chemochine.<\/p>

\u00a0<\/p>

Valentina Cecchinato, PhD, Ricercatrice associata \u2013 Nel corso degli ultimi anni, una linea di ricerca indipendente \u00e8 stata sviluppata all\u2019interno del gruppo da Valentina Cecchinato, la quale studia come le alterazioni del sistema delle chemochine possano influenzare la progressione della malattia da HIV-1. L\u2019infezione da HIV-1, se non trattata, provoca un graduale deterioramento del sistema immunitario, portando allo sviluppo della sindrome da immunodeficienza acquisita (AIDS). Sebbene la terapia antiretrovirale sia altamente efficace nel trattamento dell\u2019infezione, essa non \u00e8 in grado di eradicare completamente il virus, che sfugge al controllo del sistema immunitario nascondendosi in vari organi. Alterazioni persistenti del sistema immunitario e uno stato di infiammazione cronica riducono la capacit\u00e0 dell\u2019individuo di combattere efficacemente altre malattie e di rispondere in modo appropriato ai vaccini.<\/p>

Recentemente, abbiamo scoperto la presenza di autoanticorpi contro specifiche chemochine in persone con infezione da HIV. I nostri studi mirano a determinare in che modo questi autoanticorpi contribuiscano alla progressione della malattia, o riducendo l\u2019infiammazione cronica, o compromettendo le risposte immunitarie e facilitando cos\u00ec l\u2019immunodeficienza.<\/p>

Questa ricerca potrebbe aprire la strada a ulteriori studi preclinici volti a valutare l\u2019efficacia di terapie mirate alle chemochine per ridurre la diffusione virale e ripristinare le risposte immunitarie durante l\u2019infezione da HIV.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Group Leader<\/p>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Mariagrazia Uguccioni<\/strong><\/a>
mariagrazia.uguccioni@irb.usi.ch<\/a>
+41 58 666 7250<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Pubblicazioni<\/span><\/a><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Valentina Cecchinato<\/a><\/span>
Gabriela Danelon – Sargenti<\/a><\/span>
Veronica Martini<\/a>
Alessandro Mesaglio<\/a><\/span>
Claudia Rivoletti<\/a>
Lucia Vincenzetti<\/a><\/span><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Progetti<\/p>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Researchers
<\/strong>Mariagrazia Uguccioni<\/a><\/span> – Group Leader
Gabriela Danelon Sargenti<\/a><\/span> – Technician

Status: <\/strong>in progress<\/p>

Overview<\/strong><\/p><\/section>

Chemokines have emerged as key controllers of integrin function and cell locomotion. A vast range of\u00a0in\u00a0situ<\/em>\u00a0experiments has revealed that a variety of chemokines can be concomitantly produced in physiology, as well as in tumours. This renders the chemokine system a good target for therapy, and has increased the search, by pharmaceutical companies, for chemokine antagonists. While we understand well the effects of different chemokines one by one, much less was known about the potential consequences of the expression of multiple chemokines, cytokines, toll like receptor ligands or different inflammatory molecules, on cell responses to chemokines. Chemokine structure\/function studies led us to identify chemokines that can act as natural antagonists by preventing natural agonist binding and the subsequent activation of the receptor. Recently, we have described chemokines that can act in synergism with chemokine receptor agonists, forming heterocomplexes able to induce functional responses at lower agonist concentration. There is no more doubt that the synergism between chemokines is crucial at the very early stage of inflammation, while the study of the role of molecules, such as the alarmin High Mobility Group Box 1 (HMGB1), that can synergise with chemokines is at its infancy.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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Researchers
<\/strong>Mariagrazia Uguccioni<\/a><\/span> – Group Leader
Gabriela Danelon Sargenti<\/a><\/span> – Technician<\/p>

Status: <\/strong>in progress<\/p>

Overview<\/strong><\/p><\/section>

We have recently provided evidence that HMGB1, a damage associated molecular pattern protein (DAMP), can synergise with the CXCR4 agonist, CXCL12, promoting immune cell influx in injured tissues and enhancing immune cell responses. Cell income is blocked by glycyrrhizin, the sweet tasting compound of liquorice root, able to abolish the synergistic effect of HMGB1 on CXCL12-dependent migration, without affecting CXCL12\/CXCR4 interaction. Given the fact that CXCL12 is strongly expressed in many tissues, favouring cell influx and egression, we aim to characterize\u00a0in vitro<\/em>\u00a0and\u00a0in vivo<\/em>\u00a0the mechanisms of action of chemokine synergy-inducing molecules on cell trafficking.<\/p>

These studies might pave the way to establish novel approaches for controlling leukocyte migration and activities.<\/p><\/section><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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Group leaders:\u00a0Mariagrazia Uguccioni<\/a><\/strong>
Researchers: Valentina Cecchinato<\/a> – Scientist, Gabriela Danelon Sargenti<\/a> – Technician<\/strong>
Status:\u00a0In progress<\/strong><\/p><\/section>

Researchers
<\/strong>Mariagrazia Uguccioni<\/a><\/span> – Group Leader
Valentina Cecchinato<\/a><\/span> – Scientist
Gabriela Danelon Sargenti<\/a><\/span> – Technician

Status: <\/strong>in progress<\/p>

Overview<\/strong><\/p>

30 years after the discovery of human immunodeficiency virus (HIV) as the causative agent of AIDS, the mechanisms governing pathogenesis and disease progression are still not fully understood. Indeed, a progressive impairment of the immune system, with alterations that affect both innate and adaptive immunity, characterizes the infection with HIV\u20111 in humans and with simian immunodeficiency virus (SIV) in macaques. It has been proposed that a state of chronic immune activation contributes to the loss of CD4+<\/sup>\u00a0T\u00a0cells and to alterations of immune responses, ultimately leading to disease progression.<\/p>

The loss of CD4+<\/sup>CCR5+<\/sup>\u00a0T\u00a0cells in the gut associated lymphoid tissue (GALT) has been well documented both in the natural host and in pathogenic models of SIV infection. A decrease in the frequency of Th17 cells, a subset of effector T\u00a0cells involved in the immune response against extracellular bacteria, has been described by Dr. Cecchinato in the mucosa of SIV infected animals. Nevertheless, the migratory capacity of this T\u00a0cell subpopulation has not been investigated so far.<\/p>

Chemokines are important mediators of leukocyte trafficking and function, and deregulation of their expression might contribute in part to the pathogenesis of HIV-1\/SIV infection. In the frame of a projects funded by the European Community and by the Swiss HIV Cohort Study, we are investigating the mechanisms that mediate CCR6+<\/sup>\/Th17 cells trafficking and activities at mucosal sites together with their decrease in frequency during HIV\/SIV infection in order to better understand the pathogenesis of AIDS and in view of generating efficient vaccines.<\/p><\/section><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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Chemokine ed Immunit\u00e0 Panoramica Il nostro interesse di ricerca rimane focalizzato sul traffico cellulare nella fisiologia e patologia umana, con particolare attenzione ai meccanismi che regolano la modulazione dell\u2019espressione e dell\u2019attivit\u00e0 delle chemochine, molecole chiave nel controllo della migrazione cellulare, e dei loro recettori. Gli effetti delle chemochine sono mediati da recettori a sette domini […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"elementor_header_footer","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"class_list":["post-22328","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"\nChemochine ed immunit\u00e0 - IRB USI<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/irb.usi.ch\/it\/chemochine-ed-immunita\/\" \/>\n<meta property=\"og:locale\" content=\"it_IT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Chemochine ed immunit\u00e0 - IRB USI\" \/>\n<meta property=\"og:description\" content=\"Chemokine ed Immunit\u00e0 Panoramica Il nostro interesse di ricerca rimane focalizzato sul traffico cellulare nella fisiologia e patologia umana, con particolare attenzione ai meccanismi che regolano la modulazione dell\u2019espressione e dell\u2019attivit\u00e0 delle chemochine, molecole chiave nel controllo della migrazione cellulare, e dei loro recettori. 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