The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity

被引：50

作者：

Cavalli, Giulio ^{[1
,2
,3
,4
]}

Tengesdal, Isak W. ^{[1
,2
]}

Gresnigt, Mark ^{[1
,2
,5
]}

Nemkov, Travis ^{[6
]}

Arts, Rob J. W. ^{[1
]}

Dominguez-Andres, Jorge ^{[1
]}

Molteni, Raffaella ^{[3
]}

Stefanoni, Davide ^{[4
]}

Cantoni, Eleonora ^{[4
]}

Cassina, Laura ^{[3
]}

Giugliano, Silvia ^{[7
]}

Schraa, Kiki ^{[1
]}

Mills, Taylor S. ^{[8
]}

Pietras, Eric M. ^{[8
]}

Eisenmensser, Elan Z. ^{[6
]}

Dagna, Lorenzo ^{[4
,9
]}

Boletta, Alessandra ^{[3
]}

D'Alessandro, Angelo ^{[6
]}

Joosten, Leo A. B. ^{[1
]}

Netea, Mihai G. ^{[1
,10
]}

Dinarello, Charles A. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Dept Med, Med Ctr, Nijmegen, Netherlands

[2] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA

[3] IRCCS San Raffaele Sci Inst, Div Genet & Cell Biol, Milan, Italy

[4] Univ Vita Salute San Raffaele, Milan, Italy

[5] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Microbial Pathogenic Mech, Jena, Germany

[6] Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA

[7] Humanitas Clin & Res Ctr IRCCS, Lab Mucosal Immunol & Microbiota, Via Manzoni 56, I-20089 Rozzano, MI, Italy

[8] Univ Colorado Denver, Dept Med, Div Hematol, Aurora, CO 80045 USA

[9] IRCCS San Raffaele Hosp, Unit Immunol Rheumatol Allergy & Rare Dis, Milan, Italy

[10] Univ Bonn, Life & Med Sci Inst, Dept Immunol & Metab, Bonn, Germany

来源：

CELL REPORTS | 2021年 / 35卷 / 01期

关键词：

INNATE INFLAMMATION; IL-37; BLOCKADE; FAMILY; HYPERINFLAMMATION; SUPPRESSION; PROTECTION; COVID-19; EFFICACY; SIGNAL;

D O I：

10.1016/j.celrep.2021.108955

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post-translational modifications, which enhance production of pro-inflammatory cytokines. As aberrant activation of TI is implicated in inflammatory diseases, tight regulation is critical; however, the mechanisms responsible for this modulation remain elusive. Interleukin-37 (IL-37) is an anti-inflammatory cytokine that curbs inflammation and modulates metabolic pathways. In this study, we show that administration of recombinant IL-37 abrogates the protective effects of TI in vivo, as revealed by reduced host pro-inflammatory responses and survival to disseminated candidiasis. Mechanistically, IL-37 reverses the immunometabolic changes and histone post-translational modifications characteristic of TI in monocytes, thus suppressing cytokine production in response to infection. IL-37 thereby emerges as an inhibitor of TI and as a potential therapeutic target in immune-mediated pathologies.

引用

页数：14

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