IL-36 Receptor Antagonist with Special Emphasis on IL-38

Shaik, Y.B.; Sabatino, G.; Maccauro, Giulio; Varvara, Giuseppe; Murmura, Giovanna; Saggini, Andrea; Rosati, M; Conti, Francesca; Cianchetti, Ettore; Caraffa, Auro; Antinolfi, Pierluigi; Pandolfi, Franco; Potalivo, Gabriele; Galzio, Renato; Conti, Pio; Tc, Theoharides

doi:10.1177/039463201302600103

Cited by 19 publications

(13 citation statements)

References 69 publications

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“…19,21,23,25 In contrast, IL-36Ra and IL-38 competitively bind to IL-36R, but they cannot engage IL-1RAcP, thus they function as antagonists for IL-36R signaling. [26][27][28] Recently, IL-36 cytokines have been found to promote neutrophil infiltration in psoriasis through inducing neutrophil chemokine production from keratinocytes. 29 However, whether they play a role in neutrophilic inflammation in CRS is not known.…”

mentioning

confidence: 99%

The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

Wang

Jiang

et al. 2018

Journal of Allergy and Clinical Immunology

158

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confidence: 99%

The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

Wang

Jiang

et al. 2018

Journal of Allergy and Clinical Immunology

158

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“…IL-36 is another proinflammatory family member of IL-1 and a common mediator of innate and adaptive immune responses. It is inhibited by IL-36Ra 64 and uses mitogen-activated protein kinase and nuclear factor kB pathways, exerting proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor, as does IL-36Ra, and has similar biological effects on immune cells.…”

Section: Il-36mentioning

confidence: 99%

Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

Akdiş

Aab

Altunbulakli

et al. 2016

Journal of Allergy and Clinical Immunology

689

617

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There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.

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“… 4,14,15 Elevated IL-36α mRNA and protein expression was reported also in chronic kidney disease. 16 IL-36R signaling may contribute to inflammation and tissue homeostasis in rheumatoid arthritis, psoriatic arthritis, 17 asthma, chronic obstructive pulmonary disease 18 and inflammatory bowel diseases. 19-21 Initial support for a role of IL-36R signaling in driving epithelial-mediated inflammation stemmed from findings demonstrating that transgenic mice overexpressing IL-36α in keratinocytes exhibit inflammatory skin lesions with some features common to human psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies

Ganesan

Raymond

Mennerich

et al. 2017

mAbs

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Deficiency of interleukin (IL)-36 receptor antagonist (DITRA) syndrome is a rare autosomal recessive disease caused by mutations in IL36RN. IL-36R is a cell surface receptor and a member of the IL1R family that is involved in inflammatory responses triggered in skin and other epithelial tissues. Accumulating evidence suggests that IL-36R signaling may play a role in the pathogenesis of psoriasis. Therapeutic intervention of IL-36R signaling offers an innovative treatment paradigm for targeting epithelial cell-mediated inflammatory diseases such as the life-threatening psoriasis variant called generalized pustular psoriasis (GPP). We report the discovery and characterization of MAB92, a potent, high affinity anti-human IL-36 receptor antagonistic antibody that blocks human IL-36 ligand (α, β and γ)-mediated signaling. In vitro treatment with MAB92 directly inhibits human IL-36R-mediated signaling and inflammatory cytokine production in primary human keratinocytes and dermal fibroblasts. MAB92 shows exquisite species specificity toward human IL-36R and does not cross react to murine IL-36R. To enable in vivo pharmacology studies, we developed a mouse cross-reactive antibody, MAB04, which exhibits overlapping binding and pharmacological activity as MAB92. Epitope mapping indicates that MAB92 and MAB04 bind primarily to domain-2 of the human and mouse IL-36R proteins, respectively. Treatment with MAB04 abrogates imiquimod and IL-36-mediated skin inflammation in the mouse, further supporting an important role for IL-36R signaling in epithelial cell-mediated inflammation.

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IL-36 Receptor Antagonist with Special Emphasis on IL-38

Cited by 19 publications

References 69 publications

The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis

Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies

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