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Dans une \u00e9tude r\u00e9cente, des chercheuses et des chercheurs de l\u2019Institut Necker Enfants Malades, ont r\u00e9v\u00e9l\u00e9 qu\u2019un type de cellules immunitaires dans la rate \u2014 les macrophages r\u00e9sidents de la zone marginale de la rate (MMMs) \u2014 joue un r\u00f4le crucial dans l\u2019activation de la r\u00e9ponse immunitaire contre les cellules tumorales circulant dans le sang. Une d\u00e9couverte qui remet en question certaines id\u00e9es re\u00e7ues sur le fonctionnement du syst\u00e8me immunitaire.<\/p>\n<\/div>\n<\/div>\n<\/div>\n
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Coupe 2D d\u2019une rate de souris observ\u00e9e 24 h apr\u00e8s immunisation avec un antig\u00e8ne mod\u00e8le (Ovalbumine), cibl\u00e9 vers les macrophages m\u00e9tallophiles (MMMs). L\u2019image montre des contacts (en jaune) entre les MMMs (en vert) et des lymphocytes T sp\u00e9cifiques de l\u2019ovalbumine activ\u00e9s (CD69, en rouge), sans contact avec les cellules dendritiques (en cyan).<\/p>\n
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\u00a9 Mauvais FX et al.,<\/i>\u00a0Immunity 2025 \/\u00a0Institut Necker Enfants Malades, UMR-S 1151<\/p>\n<\/div>\n<\/div>\n<\/div>\n
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Les macrophages sont des cellules cl\u00e9s de notre syst\u00e8me immunitaire. Ils ing\u00e8rent et d\u00e9truisent les corps \u00e9trangers, les pathog\u00e8nes et les cellules en fin de vie, jouant ainsi un r\u00f4le crucial dans l\u2019immunit\u00e9 inn\u00e9e.<\/p>\n
Mais certains macrophages, plus sp\u00e9cialis\u00e9s, restent peu \u00e9tudi\u00e9s, en partie \u00e0 cause de la difficult\u00e9 de les isoler. C\u2019est le cas des macrophages r\u00e9sidents de la zone marginale de la rate, ou MMMs. Ces cellules occupent une position strat\u00e9gique pour d\u00e9tecter et intercepter les menaces en circulation dans le sang circulant.<\/p>\n
Jusqu\u2019ici, les MMMs \u00e9taient consid\u00e9r\u00e9s comme de simples \u00ab\u00a0pi\u00e8ges \u00e0 microbes\u00a0\u00bb, capturant les pathog\u00e8nes ou les cellules tumorales sans jouer un r\u00f4le direct dans l\u2019activation des cellules immunitaires adaptatives. On pensait que seules quelques cellules dendritiques, sp\u00e9cialis\u00e9es dans la d\u00e9tection initiale des menaces, pouvaient activer les lymphocytes \u00ab\u00a0killer\u00a0\u00bb T CD8+, charg\u00e9s d\u2019\u00e9liminer les cellules infect\u00e9es ou canc\u00e9reuses.<\/p>\n
Mais gr\u00e2ce \u00e0 une technique innovante de purification, les chercheuses et les chercheurs ont r\u00e9ussi \u00e0 isoler des MMMs \u00ab purs \u00bb et montr\u00e9 qu\u2019ils sont capables d\u2019activer directement les lymphocytes T CD8+ via un m\u00e9canisme appel\u00e9 cross-priming<\/em> (ou pr\u00e9sentation crois\u00e9e).<\/p>\n \u00c0 l\u2019aide de techniques d\u2019imagerie en feuillets de lumi\u00e8re \u00e0 l\u2019\u00e9chelle de la rate enti\u00e8re ou d\u2019imagerie intravitale, ils ont observ\u00e9 in situ<\/em> des interactions prolong\u00e9es entre MMMs et lymphocytes T CD8+ au sein de la rate.<\/p>\n Pour activer les lymphocytes T, les MMMs utilisent une voie intracellulaire dite \u00ab vacuolaire \u00bb, faisant intervenir des compartiments intracellulaires sp\u00e9cialis\u00e9s, pour produire des fragments de peptides capables de stimuler les lymphocytes T CD8+. Cette voie est diff\u00e9rente de celle des cellules dendritiques (qui utilisent une voie cytosolique). Cette voie \u00ab\u00a0vacuolaire\u00a0\u00bb, g\u00e9n\u00e9ralement jug\u00e9e moins performante, se r\u00e9v\u00e8le ici particuli\u00e8rement efficace.<\/p>\n Fait marquant\u00a0: m\u00eame en l\u2019absence de cellules dendritiques r\u00e9put\u00e9es indispensables pour activer les lymphocytes \u00ab\u00a0killer\u00a0\u00bb, les MMMs parviennent \u00e0 d\u00e9clencher une r\u00e9ponse antitumorale robuste dans des mod\u00e8les murins. Cette capacit\u00e9 d\u00e9pend toutefois de Batf3, un facteur de transcription \u00e9galement impliqu\u00e9 dans le d\u00e9veloppement et les fonctions du type de cellules dendritiques efficace pour la pr\u00e9sentation crois\u00e9e.<\/p>\n Les chercheuses et les chercheurs ont confirm\u00e9 ce r\u00f4le dans diff\u00e9rents mod\u00e8les exp\u00e9rimentaux, d\u00e9montrant une protection contre des m\u00e9tastases pulmonaires et des leuc\u00e9mies exp\u00e9rimentales.<\/p>\n Bien que peu abondants au sein de la rate, les MMMs se r\u00e9v\u00e8lent \u00eatre des acteurs majeurs de l\u2019immunit\u00e9 antitumorale. Leur capacit\u00e9 \u00e0 capter les cellules tumorales et \u00e0 d\u00e9clencher une r\u00e9ponse cytotoxique sans relais obligatoire par les cellules dendritiques en fait des candidats prometteurs pour de futures strat\u00e9gies th\u00e9rapeutiques visant \u00e0 renforcer la surveillance immunitaire contre les tumeurs circulantes ou envahissant la rate.<\/p>\n Mauvais FX, Hamel Y, Silvin A, Mulder K, Hildner K, Akyol R, Dalod M, Koumantou D, Saveanu L, Garfa M, Cagnard N, Bertocci B, Ginhoux F, van Endert P. Metallophilic marginal zone macrophages cross-prime CD8+\u00a0T\u00a0cell-mediated protective immunity against blood-borne tumors. Immunity. 2025 Mar 18:S1074-7613(25)00094-9. doi: 10.1016\/j.immuni.2025.02.027. Epub ahead of print. PMID: 40139188.<\/p>\n L’article est accessible en cliquant ici.<\/a> <\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=\u00a0\u00bb1_4″][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section bb_built=\u00a0\u00bb1″ specialty=\u00a0\u00bboff\u00a0\u00bb _builder_version=\u00a0\u00bb3.21″ custom_padding=\u00a0\u00bb0px||0px|\u00a0\u00bb prev_background_color=\u00a0\u00bb#000000″ inner_width=\u00a0\u00bbauto\u00a0\u00bb inner_max_width=\u00a0\u00bbnone\u00a0\u00bb][et_pb_row _builder_version=\u00a0\u00bb3.19.11″ width=\u00a0\u00bb80%\u00a0\u00bb max_width=\u00a0\u00bb1080px\u00a0\u00bb][et_pb_column type=\u00a0\u00bb4_4″][et_pb_text admin_label=\u00a0\u00bb\u00c0 lire aussi\u00a0\u00bb _builder_version=\u00a0\u00bb3.21″]<\/p>\n [\/et_pb_text][et_pb_blog _builder_version=\u00a0\u00bb3.21″ posts_number=\u00a0\u00bb4″ include_categories=\u00a0\u00bb13″ show_author=\u00a0\u00bboff\u00a0\u00bb show_date=\u00a0\u00bboff\u00a0\u00bb show_pagination=\u00a0\u00bboff\u00a0\u00bb border_width_bottom_fullwidth=\u00a0\u00bb1px\u00a0\u00bb border_color_bottom_fullwidth=\u00a0\u00bbrgba(51,51,51,0.18)\u00a0\u00bb custom_padding=\u00a0\u00bb||50px|\u00a0\u00bb module_id=\u00a0\u00bbpage_type_blog\u00a0\u00bb header_level=\u00a0\u00bbh4″ \/][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>\n","protected":false},"excerpt":{"rendered":"Les r\u00e9sultats montrent que les MMMs ne sont pas de simples cellules sentinelles passives, mais qu\u2019ils peuvent eux-m\u00eames d\u00e9clencher une r\u00e9ponse immunitaire cytotoxique efficace. <\/em><\/h3>\n
Un m\u00e9canisme diff\u00e9rent\u2026mais efficace<\/h2>\n
Une activation ind\u00e9pendante des cellules dendritiques<\/h2>\n
Vers de nouvelles pistes th\u00e9rapeutiques ?<\/h2>\n
Retrouvez l’article dans son int\u00e9gralit\u00e9<\/h2>\n
\u00c0<\/span> lire aussi<\/h2>\n