- M2 macrophages generate hyporesponsive NK cells through overexpression of the inhibitory receptor CD85j

NÚÑEZ, SOL YANEL; ZIBLAT, ANDREA; SECCHIARI, FLORENCIA; SIERRA, JESSICA MARIEL; TORRES, NICOLÁS IGNACIO; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; ZWIRNER, NORBERTO WALTER

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias y 64a Reunión Anual de la Sociedad Argentina de Inmunología; 2017

Sociedad Argentina de Inmunología

Upon activation, macrophages can become pro-inflammatory (M1) or anti-inflammatory (M2) cells. Moreover, NK cells are critical players during immunity against tumors. Previously, we interrogated the consequences of the crosstalk between M2 and NK cells and demonstrated that M2 macrophages inhibit IFN- secretion through TGF- secretion and NK cell degranulation and cytotoxicity against tumor cells in a contact dependent manner but independent of TGF-. To further get insight into the negative regulation of NK cell-mediated cytotoxicity by M2, here we investigated the underlying mechanisms involved in this inhibition. Accordingly, human monocytes were differentiated to unpolarized macrophages (M0) with M-CSF for 6 days and then exposed overnight to LPS and IFN- or IL-4 to obtain M1 and M2, respectively. These cells were then co-cultured overnight with isolated NK cells. A phenotypic characterization of NK cells cultured with M1 or M2 revealed no differences in the expression of the activating receptors CD16, DNAM-1, NKp46, NKp44, NKp30, NKG2D, NKp80 and NKG2C (n>7) but we observed an overexpression of the inhibitory receptor CD85j (ILT-2) in NK cells co-cultured with M2 compared to M1 (n=6, p