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M‐CSF induces the expression of a membrane‐bound form of IL ‐18 in a subset of human monocytes differentiating in vitro toward macrophages
Author(s) -
Bellora Francesca,
Castriconi Roberta,
Doni Andrea,
Cantoni Claudia,
Moretta Lorenzo,
Mantovani Alberto,
Moretta Alessandro,
Bottino Cristina
Publication year - 2012
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201142173
Subject(s) - cd16 , cd14 , biology , inflammasome , microbiology and biotechnology , proinflammatory cytokine , immune system , cytokine , monocyte , in vitro , immunology , inflammation , biochemistry , cd8 , cd3
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‐CSF induces the expression of a membrane‐bound form of IL ‐18 (m IL ‐18) in a subset of human blood monocytes differentiating toward macrophages. While monocytes, DC , and GM‐CSF ‐treated monocytes did not express m IL ‐18, its expression was detected in approximately 30–40% of M‐CSF ‐primed macrophages differentiating from both CD 16 − and CD 16 + monocytes. Treatment with the caspase‐1 inhibitor significantly reduced m IL ‐18 expression suggesting the requirement of an assembled inflammasome for IL ‐18 surface expression. Polarization toward M 2 did not modify m IL ‐18 expression. On the contrary, LPS stimulation of both M 0 and M 2 (m IL ‐18 + ) macrophages induced shedding of m IL ‐18, which was likely mediated by the activation of cellular protease(s). Importantly, the soluble form IL ‐18 (s IL ‐18) induced in autologous resting NK cells both the expression of CCR 7 and the production of high amounts of IFN ‐γ, which was virtually abrogated by Ab‐mediated neutralization of s IL ‐18. Overall our data shed new light on the cells and mechanisms leading to the release of s IL ‐18, the major IFN ‐γ‐inducing factor in both physiological and pathological immune responses.