title: IL-34- and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α.
abstract: Macrophages orchestrate the immune response via the polarization of CD4(+) T helper (Th) cells. Different subsets of macrophages with distinct phenotypes, and sometimes opposite functions, have been described. M-CSF and IL-34 induce the differentiation of monocytes into IL-10(high) IL-12(low) immunoregulatory macrophages, which are similar to tumor-associated macrophages (TAMs) in ovarian cancer. In this study, we evaluated the capacity of human macrophages induced in the presence of M-CSF (M-CSF macrophages) or IL-34 (IL-34 macrophages) and ovarian cancer TAMs to modulate the phenotype of human CD4(+) T cells. Taken together, our results show that M-CSF-, IL-34 macrophages, and TAMs switch non-Th17 committed memory CD4(+) T cells into conventional CCR4(+) CCR6(+) CD161(+) Th17 cells, expressing or not IFN-gamma. Contrary, the pro-inflammatory GM-CSF macrophages promote Th1 cells. The polarization of memory T cells into Th17 cells is mediated via membrane IL-1α (mIL-1α), which is constitutively expressed by M-CSF-, IL-34 macrophages, and TAMs. This study elucidates a new mechanism that allows macrophages to maintain locally restrained and smoldering inflammation, which is required in angiogenesis and metastasis.
authors.affiliation: Université d'Angers, Angers, France; Inserm, unit 892, Angers, France; CNRS, unit 6299, Angers, France; LabEx IGO "Immunotherapy, Graft, Oncology", Angers, France.
authors.forename: Etienne D
authors.initials: ED
authors.lastname: Foucher
authors.forename: Simon
authors.initials: S
authors.lastname: Blanchard
authors.forename: Laurence
authors.initials: L
authors.lastname: Preisser
authors.forename: Philippe
authors.initials: P
authors.lastname: Descamps
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism; D053765:Interleukin-12 Subunit p35 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D053582:Interleukin-1alpha / Q000276:immunology*; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology; D054398:Receptors, CCR4 / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: C515354:CCR4 protein, human; C106311:CCR6 protein, human; C508609:IL10 protein, human; C508858:IL12A protein, human; C508584:IL1A protein, human; C529076:IL34 protein, human; D053765:Interleukin-12 Subunit p35; D020381:Interleukin-17; D053582:Interleukin-1alpha; D007378:Interleukins; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054398:Receptors, CCR4; D054399:Receptors, CCR6; D016753:Interleukin-10; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: IL-1α; IL-34; Inflammation; M-CSF; Macrophages; Th17 cells