IL-34- and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α

Etienne D. Foucher (1, 2) , Simon J. Blanchard (1, 2) , Laurence Preisser (1, 2) , Philippe Descamps (1, 2) , Norbert Ifrah (1, 2) , Yves Delneste (1, 2) , Pascale Jeannin (1, 2) , Etienne D Foucher (1, 2)

1 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
2 LabEX IGO Immunothérapie Grand Ouest

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-10high IL-12low 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.

Mots clés: Macrophages; M-CSF; IL-34; IL-1α; Th17

Domaines: Immunité innée; Immunité adaptative

Etienne D. Foucher, Simon J. Blanchard, Laurence Preisser, Philippe Descamps, Norbert Ifrah, et al.. IL-34- and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α. European Journal of Immunology, 2015, 45 (4), pp.1092-1102. ⟨10.1002/eji.201444606⟩. ⟨hal-01392241⟩