IL-37 inhibits the maturation of dendritic cells through the IL-1R8-TLR4-NF-κB pathway

Liu, Tianxiao; Liu, Jing; Lin, Yingzhong; Qu, Bin; Chang, Chao; Zhang, Jianwei; Liang, Zhongxing; Gao, Xiaonan; Liu, Shangwei; Liu, Ling; Li, Dazhu; Ji, Qingwei

doi:10.1016/j.bbalip.2019.05.009

Cited by 43 publications

(31 citation statements)

References 46 publications

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“…Similarly, the differentiation and maturation of immune cells may promote the secretion of various inflammatory factors, which is closely linked to hypertension development (15,31,32). Combined with a previous result by our group indicating that IL-37 may have a regulatory role in the differentiation and maturation of various immune cells and the release of inflammation-associated factors (13,33), it was hypothesized that IL-37 may be involved in the process of hypertension through regulation of inflammatory effects, similar to those that occur in other cardiovascular diseases. The specific role and mechanisms remain to be fully elucidated and still require to be deter- ------------------------------------------------------------------------------------------------------------------------------------------------------------- Hypertension may be divided into dipper hypertension and non-dipper hypertension depending on how much the blood pressure drops at night.…”

Section: Univariatesupporting

confidence: 66%

“…IL-37 has been the focus of recent research and increasing evidence has confirmed that it is closely associated with the progression of cardiovascular disease (9,10). IL-37 has been indicated to alleviate the progression of atherosclerosis and enhance the stability of plaques in apolipoprotein E knockout mice fed a high-fat diet by inhibiting T-lymphocyte differentiation, dendritic cell maturation and vascular smooth muscle cell apoptosis (11)(12)(13). In another study, IL-37 was reported to have no effect on atherosclerosis development in low-density lipoprotein receptor-deficient mice receiving a high-fat diet, although the local inflammation in the blood vessels was reduced (14).…”

Section: Introductionmentioning

confidence: 99%

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Circulating IL‑37 levels are elevated in patients with hypertension

Wang

et al. 2021

Exp Ther Med

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has been reported to be closely linked to vascular diseases, including atherosclerosis and aortic calcification. The present study aimed to assess the expression levels of IL-37 in patients with hypertension. Blood samples were collected from control subjects (n=20) and patients with hypertension (n=45). Subsequently, macrophages, lymphocytes and dendritic cells were individually isolated and the mRNA expression of IL-37 was measured. In addition, the circulating IL-37 levels in control subjects (n=30) and patients with hypertension (n=334) were assessed. Furthermore, all patients who were subjected to detection of circulating IL-37 underwent ambulatory blood pressure monitoring. The results suggested that the mRNA levels of IL-37 in macrophages, but not in lymphocytes and dendritic cells, isolated from patients with hypertension were markedly elevated compared with those in cells isolated from control subjects. Circulating IL-37 levels were increased in patients with hypertension compared with those in control subjects and positively correlated with systolic and diastolic blood pressure in patients with hypertension. No differences were observed between patients with dipper hypertension and patients with non-dipper hypertension. In addition, patients with hypertension with a smoking habit, type 2 diabetes mellitus and carotid atherosclerotic plaque (CAP) exhibited higher IL-37 levels. IL-37 levels were positively correlated with creatinine, C-reactive protein and homocysteine levels. Furthermore, the results of a linear regression analysis suggested that IL-37 levels were independently associated with the presence of CAP. In conclusion, IL-37 levels are increased in patients with hypertension and may be associated with the onset of CAP.

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Section: Univariatesupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Circulating IL‑37 levels are elevated in patients with hypertension

Wang

et al. 2021

Exp Ther Med

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“…Recently, our group found that DCs treated with IL-37 plus troponin I alleviate cardiac remodeling after myocardial infarction [15]. In addition, Liu et al reported that IL-37 attenuated the maturation of DCs through the IL-1R8-TLR4-NF- κ B pathway in ApoE −/− mice [45]. These two recent publications indicated that IL-37 could ameliorate atherosclerosis and cardiac remodeling after myocardial infarction in the murine model via targeting DCs.…”

Section: Discussionmentioning

confidence: 99%

IL-37 Plays a Beneficial Role in Patients with Acute Coronary Syndrome

Mao

Zhu

Zhang

et al. 2019

Mediators of Inflammation

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Background Interleukin-37 (IL-37) acts as an inhibitor of innate and adaptive immunity. However, the exact role of IL-37 in the patients with acute coronary syndrome (ACS) remains to be elucidated. Methods Patients were classified into 4 groups: normal coronary artery (NCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). The circulating Treg, Th1, and Th17 frequencies were measured. The effect of IL-37 on stimulated peripheral blood mononuclear cells (PBMCs) and the influence of IL-37 on DCs were explored. In addition, the role of IL-37-treated tDCs on Treg cell expansion and the stability of these tDCs were also tested. Results Our results showed that the circulating Treg frequencies were decreased, while Th1 and Th17 frequencies were increased in ACS patients, and that IL-37 expanded Tregs but suppressed Th1 and Th17 cells in activated PBMCs derived from ACS patients. Of note, IL-37-treated human DCs obtained a tolerogenic phenotype, and such tDCs promoted expansion of Tregs and decreased the Th1 and Th17 populations when cocultured with CD4+ T cells. Interestingly, IL-37-treated DCs from patients with ACS are phenotypically and functionally comparable to IL-37-treated DCs from NCA patients, and tolerogenic properties of IL-37-treated DCs were highly stable. Conclusion In conclusion, our results reveal a beneficial role of IL-37 in the patients with ACS and suggest that autologous IL-37-treated tDCs may be a novel therapeutic strategy for the patients with ACS.

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“…IL-37 is a member of the IL-1 gene family that broadly inhibits inflammation in various inflammatory and autoimmune diseases, while also reducing acquired immunity, paving the way for a healing effect of psoriasis [72]. In fact, the dendritic cells (DC) that express IL-37 are tolerogenic, an effect which reverberates on the activation of the responses of effector T cells, inducing Treg cells and inhibiting the adaptive immunity [73]. In rodent experiments, IL-37 has shown protection in many induced inflammatory pathologies, while also suppressing the immune response [74].…”

Section: Inhibitory Effect Of Il-37mentioning

confidence: 99%

Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra

Conti¹,

Pregliasco²,

Rg³

et al. 2021

Preprint

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Psoriasis (PS) is an autoimmune skin disease mediated by immune cells that typically presents inflammatory erythematous plaques, and it is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature and reside in vascularized tissues. They can be activated by antigen provoking overexpression of pro-inflammatory cytokines and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophage to release IL-36, a powerful pro-inflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic pro-inflammatory diseases such as psoriasis. Suppressing IL-36 results in a noticeable improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra which binds on to IL-36 receptor ligand, but suppression can also occur by binding IL-38 to the IL-36R receptor. IL-38 specifically binds only to IL-36R and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs, a process that activates macrophages to secrete pro-inflammatory IL-36 inhibited by IL-38. In this article we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis and hold promise of an innovative therapeutic tool.

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IL-37 inhibits the maturation of dendritic cells through the IL-1R8-TLR4-NF-κB pathway

Cited by 43 publications

References 46 publications

Circulating IL‑37 levels are elevated in patients with hypertension

Circulating IL‑37 levels are elevated in patients with hypertension

IL-37 Plays a Beneficial Role in Patients with Acute Coronary Syndrome

Mast Cells Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-inflammatory Cytokines IL-37, IL-38 and IL-1Ra

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