Interleukin-38 is elevated in inflammatory bowel diseases and suppresses intestinal inflammation

Xie, Congying; Yan, Wei; Quan, Runze; Chen, Chaoyue; Tu, Lei; Hou, Xiaohua; Fu, Yu

doi:10.1016/j.cyto.2019.154963

Cited by 47 publications

(43 citation statements)

References 30 publications

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“…Previous reports show that IL1F10 mRNA is predominantly present in the keratinocytes of the skin, the spleen, and proliferating B cells of the tonsil [2, 15, 35]. In colon biopsies of inflammatory bowel disease patients, IL1F10 expression was co‐localized completely with a portion of CD19 + B cells, while IL1F10 expression was not detected in CD68 + macrophages or CD3 + T cells [35]. Here, we demonstrate that IL1F10 gene expression is specific for isolated B cells from PBMC, but not total PBMC or the flow‐through that is depleted of B cells.…”

Section: Discussionmentioning

confidence: 99%

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

et al. 2020

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The IL‐1 family member IL‐38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL‐38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL‐38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19+ B cells from PBMC was lower, whereas cell‐associated IL‐38 expression was comparable. In vitro, IL‐38 is released from CD19+ B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL‐38, compared to 100‐fold induction of IL‐6 and IL‐1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL‐38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL‐38 also correlated inversely with high sensitivity C‐reactive protein (p < 0.01), IL‐6, IL‐1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL‐38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL‐38 as an anti‐inflammatory cytokine.

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Section: Discussionmentioning

confidence: 99%

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

et al. 2020

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“…Many studies have confirmed that IL‐38 is an anti‐inflammatory cytokine. It has been reported that IL‐38 may play an anti‐inflammatory role in arthritis (Boutet et al, 2017), psoriasis (Han et al, 2019; Mercurio et al, 2018), systemic lupus erythematosus (Chu et al, 2017; Rudloff et al, 2015), inflammatory bowel disease (Xie et al, 2020), sepsis (Ge, Huang, Wu, Dong, & Yao, 2020; F. Xu et al, 2018), diabetes (Liu, Chen, Zhou, Mu, & Liu, 2020), myocardial injury (Wei et al, 2020), and asthma (Matsuoka et al, 2019; Sun et al, 2020). Recently, we also found that IL‐38 has the effect of inhibiting obesity‐induced inflammation (K. Xu et al, 2019) and liver inflammatory damage (Yuan et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

Chen

Sun

et al. 2020

Cell Biology International

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Interleukin-38 (IL-38) is a novel member of the IL-1 cytokine family with anti-inflammatory activity. However, its effect on adipogenesis and inflammatory cytokines secretion of adipocytes in vitro has not been reported. To address whether IL-38 inhibits adipogenesis and inflammation in vitro, adipose precursor 3T3-L1 cells were cultured with or without IL-38. The morphology and size of lipid droplets in 3T3-L1 cells were measured by Oil red O staining. The mRNA expression levels of GATA-binding protein-3 (GATA-3), glucose transporter type 4 (GLUT4), peroxisome proliferator-associated receptor γ2, IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1) in 3T3-L1 cells were detected by real-time PCR, The contents of IL-6, IL-1β, and MCP-1 in 3T3-L1 cell medium supernatants were determined by enzyme-linked immunosorbent assay. IL-38 significantly decreased the number of lipid droplets in 3T3-L1 cells. IL-38 also increased GATA-3 and GLUT4 mRNA expression and inhibited IL-1β, IL-6, and MCP-1 secretion by 3T3-L1 cells. It is concluded that IL-38 can inhibit the differentiation of human adipocytes and inflammatory cytokine production by 3T3-L1 cells.

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“…Interestingly, administration of recombinant IL-38 effectively decreased intestinal inflammation in murine models. 67 The use of antibodies to target human IL-1RAcP (IL1R3) has been evaluated in multiple pre-clinical trial models. This targeted approach is thought to have a broader therapeutic impact on inflammatory diseases driven by certain cytokines from the IL-1 superfamily.…”

Section: Potential For Treating Ibd By Blocking Il-36rmentioning

confidence: 99%

“…IL-36Ra and IL-38 may regulate IL-36 receptor agonist expression by competing against IL-36 receptor agonists bind to the IL-1RL2 and function as negative regulators. 10,46,67 IL-36Ra is an anti-inflammatory cytokine encoded by the IL-36RN gene. The binding of IL-36Ra to IL-36R (Il1rl2) prevents the recruitment of IL-1RacP, resulting in the failure of IL-36R to produce a signal.…”

Section: How Can Il-36 Be Both Protective and Pathogenic?mentioning

confidence: 99%

IL‐36 cytokines and gut immunity

et al. 2021

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Interleukin 36 (IL-36) constitutes a group of cytokines that belong to the IL-1 superfamily. Emerging evidence has suggested a role of IL-36 in the pathogenesis of many inflammatory disorders. Intriguingly, in the gastrointestinal tract, IL-36 has a rather complex function. IL-36 receptor ligands are overexpressed in both animal colitis models and human IBD patients and may play both pathogenic and protective roles, depending on the context. IL-36 cytokines comprise three receptor agonists: IL-36a, IL-36b and IL-36c, and two receptor antagonists: IL-36Ra and IL-38. All IL-36 receptor agonists bind to the IL-36R complex and exert pleiotropic effects during inflammatory settings. Here, we first briefly review the processing and secretion of IL-36 cytokines. We then focus on the current understanding of the immunology effects of IL-36 in gut immunity. In addition, we also discuss the ongoing trials that aim to blockage IL-36R signalling for treating chronic intestinal inflammation and present some unexplored questions regarding IL-36 research.

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Interleukin-38 is elevated in inflammatory bowel diseases and suppresses intestinal inflammation

Cited by 47 publications

References 30 publications

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

Interleukin‐38 inhibits adipogenesis and inflammatory cytokine production in 3T3‐L1 preadipocytes

IL‐36 cytokines and gut immunity

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