Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

Arianna Calcinotto, Arianna Brevi, Marta Chesi, Roberto Ferrarese, Laura Garcia Perez, Matteo Grioni, Shaji Kumar, Victoria M. Garbitt, Meaghen E. Sharik, Kimberly J. Henderson, Giovanni Tonon, Michio Tomura, Yoshihiro Miwa, Enric Esplugues, Richard A. Flavell, Samuel Huber, Filippo Canducci, Vincent S. Rajkumar, P. Leif Bergsagel and Matteo Bellone ()
Additional contact information
Arianna Calcinotto: IRCCS San Raffaele Scientific Institute
Arianna Brevi: IRCCS San Raffaele Scientific Institute
Marta Chesi: Mayo Clinic Arizona
Roberto Ferrarese: IRCCS San Raffaele Scientific Institute
Laura Garcia Perez: Molekulare Immunologie und Gastroenterologie, Universitätsklinikum Hamburg–Eppendorf
Matteo Grioni: IRCCS San Raffaele Scientific Institute
Shaji Kumar: Mayo Clinic Rochester
Victoria M. Garbitt: Mayo Clinic Arizona
Meaghen E. Sharik: Mayo Clinic Arizona
Kimberly J. Henderson: Mayo Clinic Rochester
Giovanni Tonon: IRCCS San Raffaele Scientific Institute
Michio Tomura: Osaka Ohtani University
Yoshihiro Miwa: University of Tsukuba
Enric Esplugues: School of Medicine, and Howard Hughes Medical Institute Yale University
Richard A. Flavell: School of Medicine, and Howard Hughes Medical Institute Yale University
Samuel Huber: Molekulare Immunologie und Gastroenterologie, Universitätsklinikum Hamburg–Eppendorf
Filippo Canducci: IRCCS San Raffaele Scientific Institute
Vincent S. Rajkumar: Mayo Clinic Rochester
P. Leif Bergsagel: Mayo Clinic Arizona
Matteo Bellone: IRCCS San Raffaele Scientific Institute

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07305-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07305-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07305-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().