Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.
Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.
复制标题
DOI：
10.1038/s41551-023-01050-0
复制
发表时间：
2023-09
影响因子：
28.1
通讯作者：
中科院分区：
文献类型：
--
作者：
Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications. A nanoparticle integrating a fusion protein of apolipoprotein A1 and interleukin-4 and that targets myeloid-cell-rich haematopoietic organs resolves immunoparalysis in ex vivo and in vivo models of sepsis.
登录
查看更多内容
影响因子：
18.3
作者：
Mulder, Willem J. M.;Strijkers, Gustav J.;Van Tilborg, Geralda A. F.;Cormode, David P.;Fayad, Zahi A.;Nicolay, Klaas
通讯作者：
Nicolay, Klaas
影响因子：
--
作者：
Langmead, Ben
通讯作者：
Langmead, Ben
影响因子：
--
作者：
Bekkering, Siroon;Blok, Bastiaan A.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
8.8
作者：
Keating, Samuel T.;Groh, Laszlo;Riksen, Niels P.
通讯作者：
Riksen, Niels P.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK