The IL-20 subfamily of cytokines — from host defence to tissue homeostasis

Rutz, Sascha; Wang, Xiaoting; Ouyang, Wenjun

doi:10.1038/nri3766

Cited by 290 publications

(304 citation statements)

References 193 publications

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“…Interestingly, in newborn monocytes, MIF silencing reduces the production of proinflammatory cytokines but also reduces the production of cytokines with antiinflammatory and tissue repair activities such as IL-10 (53), IL-20 (54), and IL-27 (55). This suggests an important role of MIF in initiation, amplification, and termination of inflammatory responses triggered by microbial products, and more globally in fine-tuning of immune responses.…”

Section: Discussionmentioning

confidence: 99%

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

Roger

Schneider

Weier

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.newborns | Escherischia coli | prostaglandin | adenosine | sepsis

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Section: Discussionmentioning

confidence: 99%

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

Roger

Schneider

Weier

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…recently been reassigned to the IL-20 cytokine subfamily, 6 with whose other members it shares considerable structural homology. 6,7 The IL-22 gene is located on chromosome 12q15 in humans and chromosome 10 in mice.…”

Section: Introduction and Aimmentioning

confidence: 99%

“…6,7 The IL-22 gene is located on chromosome 12q15 in humans and chromosome 10 in mice. 5 Human IL-22 is expressed as a 179-amino-acid protein, sharing reasonably high homology with its murine counterpart (79%) as well as 25% homology with IL-10.…”

Section: Introduction and Aimmentioning

confidence: 99%

Profile of interleukin-22 in gut mucosal health and disease

Foxall¹,

Fernandes²,

Sousa³

2016

IJICMR

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is produced by both innate and adaptive immune cells and specifically targets nonhematopoietic cells; this provides a unique mechanism linking host immunity to mucosal homeostasis and led to its establishment as a key player in the maintenance of barrier integrity at mucosal sites particularly in the gut. Our aim is to provide an overview of the role of this cytokine in maintaining gut mucosal homeostasis in the steady state and in disease. IL-22 has two main functions in healthy states: to help shape the gut microbial flora via the induction of mucins and antimicrobial peptides and to maintain barrier integrity through the induction of epithelial cell proliferation and/or survival. Given the risk of malignancy related to uncontrolled cell growth per se, it is not surprising that the expression of this cytokine is tightly regulated by a complex interactive signaling network. This consists of a combination of cytokines and various environmental signals that can be derived directly from the diet and/or the gut microbiota. A role for IL-22 in response to gut infection has been reported. Here, we will focus specifically on how reduced levels of this cytokine can exacerbate disease pathology, as in the case of human immunodeficiency virus infection. We will also review its association with inflammatory bowel disease, where its net contribution likely reflects the balance between its pro-and anti-inflammatory functions, as well as its role in malignancy, specifically colorectal cancer. Finally, we will briefly discuss the potential pros and cons of targeting IL-22 in these, and other, clinical situations.

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“…Interleukin-22 (IL-22) is a member of the IL-10 family of cytokines and is predominantly expressed by innate lymphoid cells and activated CD4+ T helper subsets such as T helper type 17 (TH17) and TH22 cells [6,7]. IL-22 may exert multiple effects on the immune system and may be associated with the acute-phase response, activation of the innate immune system, induction of cell migration, inhibition of dendritic cell functions, and attenuation of allergic responses (7,8). IL-22 plays a crucial role in eliciting antimicrobial immunity and ensuring maintenance of mucosal barrier integrity within the intestine or lungs [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…IL-22 may exert multiple effects on the immune system and may be associated with the acute-phase response, activation of the innate immune system, induction of cell migration, inhibition of dendritic cell functions, and attenuation of allergic responses (7,8). IL-22 plays a crucial role in eliciting antimicrobial immunity and ensuring maintenance of mucosal barrier integrity within the intestine or lungs [8,9]. Mice deficient in IL-22 receptor and fed a highfat diet are predisposed to developing metabolic disorders [10,11].…”

Section: Introductionmentioning

confidence: 99%

Decreased circulating levels of il-22 in newly diagnosed metabolic syndrome patients

Yılmaz¹

2018

Ann Clin Anal Med

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Aim: Metabolic syndrome (MetS) is characterized by abdominal obesity, dyslipidemia, low-grade inflammation, insulin resistance, and hypertension that can lead to diabetes and cardiovascular disease. IL-22 is a member of the IL-10 cytokine family that has been shown to prevent or reverse obesity-induced glucose intolerance and insulin resistance; it also affects mucosal barrier maintenance and the prevention of endotoxemia and chronic inflammation. We determine IL-22 levels in MetS patients and whether IL-22 is associated with MetS and its components. Material and Method: In this cross-sectional study, we measured serum IL-22 in 194 patients who had been newly diagnosed with MetS; we also employed 73 control patients. We used logistic regression analyses to evaluate the association of low serum levels of IL-22 with metabolic syndrome after adjusting for potential confounders. Results: Serum IL-22 concentrations were lower in subjects with MetS than in the controls. Serum IL-22 was negatively correlated with adiposity, fasting insulin, fasting glucose, C-reactive protein, triglycerides, and body mass index; it was positively correlated with HDL cholesterol. Logistic regression analysis demonstrated an independent association between serum IL-22 and metabolic syndrome. Discussion: These data suggested that decreased IL-22 levels are associated with MetS and its components and that IL-22 may be a novel biomarker in metabolic and endocrine regulations.

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The IL-20 subfamily of cytokines — from host defence to tissue homeostasis

Cited by 290 publications

References 193 publications

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

Profile of interleukin-22 in gut mucosal health and disease

Decreased circulating levels of il-22 in newly diagnosed metabolic syndrome patients

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