Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
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Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. / Calcinotto, Arianna; Brevi, Arianna; Chesi, Marta; Ferrarese, Roberto; Garcia Perez, Laura; Grioni, Matteo; Kumar, Shaji; Garbitt, Victoria M; Sharik, Meaghen E; Henderson, Kimberly J; Tonon, Giovanni; Tomura, Michio; Miwa, Yoshihiro; Esplugues, Enric; Flavell, Richard A; Huber, Samuel; Canducci, Filippo; Rajkumar, Vincent S; Bergsagel, P Leif; Bellone, Matteo.
in: NAT COMMUN, Jahrgang 9, 03.12.2018, S. 4832.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
AU - Calcinotto, Arianna
AU - Brevi, Arianna
AU - Chesi, Marta
AU - Ferrarese, Roberto
AU - Garcia Perez, Laura
AU - Grioni, Matteo
AU - Kumar, Shaji
AU - Garbitt, Victoria M
AU - Sharik, Meaghen E
AU - Henderson, Kimberly J
AU - Tonon, Giovanni
AU - Tomura, Michio
AU - Miwa, Yoshihiro
AU - Esplugues, Enric
AU - Flavell, Richard A
AU - Huber, Samuel
AU - Canducci, Filippo
AU - Rajkumar, Vincent S
AU - Bergsagel, P Leif
AU - Bellone, Matteo
PY - 2018/12/3
Y1 - 2018/12/3
N2 - The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.
AB - The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Research Support, N.I.H., Extramural
U2 - 10.1038/s41467-018-07305-8
DO - 10.1038/s41467-018-07305-8
M3 - SCORING: Journal article
C2 - 30510245
VL - 9
SP - 4832
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
ER -