IL-18 is a proinflammatory cytokine belonging to the "IL-1 family" that has been shown to play a prominent role in the induction of type 1 immune responses. Here, we show that M-CSFinduces the expression of a membrane-bound form of IL-18 (mIL-18) in a subset of human blood monocytes differentiating toward macrophages. While monocytes, DC, and GM-CSF-treated monocytes did not express mIL-18, its expression was detected in approximately 30-40% of M-CSF-primed macrophages differentiating from both CD16(-) and CD16(+) monocytes. Treatment with the caspase-1 inhibitor significantly reduced mIL-18 expression suggesting the requirement of an assembled inflammasome for IL-18 surface expression. Polarization toward M2 did not modify mIL-18 expression. On the contrary, LPS stimulation of both M0 and M2 (mIL-18(+) ) macrophages induced shedding of mIL-18, which was likely mediated by the activation of cellular protease(s). Importantly, the soluble form IL-18 (sIL-18) induced in autologous resting NK cells both the expression of CCR7 and the production of high amounts of IFN-γ, which was virtually abrogated by Ab-mediated neutralization of sIL-18. Overall our data shed new light on the cells and mechanisms leading to the release of sIL-18, the major IFN-γ-inducing factor in both physiological and pathological immune responses.

M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages / F. Bellora, R. Castriconi, A. Doni, C. Cantoni, L. Moretta, A. Mantovani, A. Moretta, C. Bottino. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - 42:6(2012 Jun), pp. 1618-1626. [10.1002/eji.201142173]

M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages

A. Mantovani;
2012

Abstract

IL-18 is a proinflammatory cytokine belonging to the "IL-1 family" that has been shown to play a prominent role in the induction of type 1 immune responses. Here, we show that M-CSFinduces the expression of a membrane-bound form of IL-18 (mIL-18) in a subset of human blood monocytes differentiating toward macrophages. While monocytes, DC, and GM-CSF-treated monocytes did not express mIL-18, its expression was detected in approximately 30-40% of M-CSF-primed macrophages differentiating from both CD16(-) and CD16(+) monocytes. Treatment with the caspase-1 inhibitor significantly reduced mIL-18 expression suggesting the requirement of an assembled inflammasome for IL-18 surface expression. Polarization toward M2 did not modify mIL-18 expression. On the contrary, LPS stimulation of both M0 and M2 (mIL-18(+) ) macrophages induced shedding of mIL-18, which was likely mediated by the activation of cellular protease(s). Importantly, the soluble form IL-18 (sIL-18) induced in autologous resting NK cells both the expression of CCR7 and the production of high amounts of IFN-γ, which was virtually abrogated by Ab-mediated neutralization of sIL-18. Overall our data shed new light on the cells and mechanisms leading to the release of sIL-18, the major IFN-γ-inducing factor in both physiological and pathological immune responses.
IL-18; Macrophages; Monocytes; NK cells
Settore MED/04 - Patologia Generale
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/178894
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