Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis

Cannavò, Serafinella Patrizia; Bertino, Lucrezia; Salvo, Eleonora Di; Papaianni, Valeria; Ventura-Spagnolo, Elvira; Gangemi, Sebastiano

doi:10.1155/2019/7158014

Cited by 30 publications

(27 citation statements)

References 60 publications

(109 reference statements)

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“…Mouse models ( 9 , 11 , 45 , 46 ) and disease conditions where IL-33 is released, have shown that biological consequences over the immune response depend on the tissue environment ( 13 , 22 , 23 , 47 ). Different human disorders involve IL-33 as a potent trigger of inflammatory processes, such as Rheumatoid Arthritis, Systemic Sclerosis, Sjörgen Disease and Psoriasis ( 47 – 50 ). In addition, free IL-33 may act as a potent inducer of regulatory T cell (Tregs) responses ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease

et al. 2020

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Initially described as Th2 promoter cytokine, more recently, IL-33 has been recognized as an alarmin, mainly in epithelial and endothelial cells. While localized in the nucleus acting as a gene regulator, it can be also released after injury, stress or inflammatory cell death. As proinflammatory signal, IL-33 binds to the surface receptor ST2, which enhances mast cell, Th2, regulatory T cell, and innate lymphoid cell type 2 functions. Besides these Th2 roles, free IL-33 can activate CD8 + T cells during ongoing Th1 immune responses to potentiate its cytotoxic function. Celiac Disease (CD) is a chronic inflammatory disorder characterized by a predominant Th1 response leading to multiple pathways of mucosal damage in the proximal small intestine. By immunofluorescence and western blot analysis of duodenal tissues, we found an increased expression of IL-33 in duodenal mucosa of active CD (ACD) patients. Particularly, locally digested IL-33 releases active 18/21kDa fragments which can contribute to expand the proinflammatory signal. Endothelial (CD31 + ) and mesenchymal, myofibroblast and pericyte cells from microvascular structures in villi and crypts, showed IL-33 nuclear location; while B cells (CD20 + ) showed a strong cytoplasmic staining. Both ST2 forms, ST2L and sST2, were also upregulated in duodenal mucosa of CD patients. This was accompanied by increased number of CD8 + ST2 + T cells and the expression of T-bet in some ST2 + intraepithelial lymphocytes and lamina propria cells. IL-33 and sST2 mRNA levels correlated with IRF1, an IFN induced factor relevant in responses to viral infections and interferon mediated proinflammatory responses highly represented in duodenal tissues in ACD. These findings highlight the potential contribution of IL-33 and its fragments to exacerbate the proinflammatory circuit and potentiate the cytotoxic activity of CD8 + T cells in CD pathology.

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Section: Discussionmentioning

confidence: 99%

IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease

et al. 2020

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“…On the other hand, TNF-alpha, INF-gamma, and IL-17, major effectors of the Th1/Th17 responses in Pso and OP pathogenesis, stimulate the release of IL-33. Both skin lesions and unaffected skin biopsies of Pso patients ( 36 , 37 , 95 ) express high IL-33 levels ( 103 , 106 ). The rapid IL-33 release from keratinocytes after skin injury could be a crucial mechanism involved in the pathogenesis of Pso ( 107 – 110 ).…”

Section: The Role Of Il-33mentioning

confidence: 99%

“…The osteocyte-derived factor FGF-23, which inhibits PTH and promotes renal phosphorus excretion, also antagonizes some vitamin D effects. The IL-33/ST2 axis is, therefore, a PTH target that is able to both promote osteoblastic calcium deposition in the bone matrix and inhibit osteoclastogenesis ( 36 ). Increased levels of PTH induce elevation of sST2 ( 129 ).…”

Section: The Relationship Between Vitamin D and The Il-33/st2 Axis Inmentioning

confidence: 99%

“…Th17 cells also secrete RANKL directly and further induce osteoclast formation and secretion of bonedegrading enzymes leading to bone destruction (35). Many other cytokines involved in bone remodeling have recently been shown to also exert roles in the pathogenesis of Pso, including, in particular, IL-33 (36)(37)(38)(39). In addition, some treatments used in Pso might contribute to bone loss, for example, corticosteroids and cyclosporin, particularly when used systemically (18)(19)(20), whereas treatments at the systemic level aimed at reducing inflammation, e.g., biologics or methotrexate, could reduce the risk associated with osteoporotic fractures (40).…”

Section: Pathogenic Mechanisms Linking Pso and Opmentioning

confidence: 99%

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IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis

et al. 2021

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Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies.

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“…Research has confirmed that, compared to healthy controls and non-itchy or non-pain lesions, pruritic psoriatic skin contains elevated gene transcription levels of IL-17, IL-23, and IL-31 ( 28 ) and hyperalgesia psoriatic skin has higher expression levels of IL-33 ( 53 ). IL-17, IL-31, and IL-33 are all important inflammatory factors in the pathogenesis of psoriasis ( 58 ). Animal experiments have confirmed that IL-33 can induce dysfunction in sensory nerves ( 59 ).…”

Section: Innervation In Psoriasismentioning

confidence: 99%

The Role of Nociceptive Neurons in the Pathogenesis of Psoriasis

Zhang

2020

Front. Immunol.

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Psoriasis is a chronic inflammatory skin disease. Emerging evidence shows that neurogenic inflammation, induced by nociceptive neurons and T helper 17 cell (Th17) responses, has a fundamental role in maintaining the changes in the immune system due to psoriasis. Nociceptive neurons, specific primary sensory nerves, have a multi-faceted role in detecting noxious stimuli, maintaining homeostasis, and regulating the immunity responses in the skin. Therefore, it is critical to understand the connections and interplay between the nociceptive neurons and the immune system in psoriasis. Here, we review works on the altered innervation that occurs in psoriasis. We examine how these distinct sensory neurons and their signal transducers participate in regulating inflammation. Numerous clinical studies report the dysfunction of nociceptive neurons in psoriasis. We discuss the mechanism behind the inconsistent activation of nociceptive neurons. Moreover, we review how neuropeptides, involved in regulating Th17 responses and the role of nociceptive neurons, regulate immunity in psoriasis. Understanding how nociceptive neurons regulate immune responses enhances our knowledge of the neuroimmunity involved in the pathogenesis of psoriasis and may form the basis for new approaches to treat it.

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Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis

Cited by 30 publications

References 60 publications

IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease

IL-33 Alarmin and Its Active Proinflammatory Fragments Are Released in Small Intestine in Celiac Disease

IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis

The Role of Nociceptive Neurons in the Pathogenesis of Psoriasis

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