IL-1R3 blockade broadly attenuates the functions of six members of the IL-1 family, revealing their contribution to models of disease

Højen, Jesper Falkesgaard; Kristensen, Marie Louise Vindvad; McKee, Amy S.; Wade, Megan Taylor; Azam, Tania; Lunding, Lars; Graaf, Dennis M. de; Swartzwelter, Benjamin J; Wegmann, Michael; Tolstrup, Martin; Beckman, Karsten; Fujita, Mayumi; Fischer, Stephan; Dinarello, Charles A.

doi:10.1038/s41590-019-0467-1

Cited by 61 publications

(62 citation statements)

References 55 publications

(59 reference statements)

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“…The present study identified IL‐36α as a robust and early marker for kidney damage induced by increased phosphate excretion per nephron. IL‐36α is a recently identified pro‐inflammatory cytokine that belongs to the IL‐1 family and reported to contribute to the pathophysiology of several disorders associated with inflammation, including psoriasis, chronic obstructive pulmonary disease, and obesity [10,11]. Like other cytokines, IL‐36α is expressed primarily in immuno‐competent cells, but is induced in renal tubular cells in patients and rodent models with AKI and CKD [9,12].…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐36α as a potential biomarker for renal tubular damage induced by dietary phosphate load

et al. 2020

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Excessive intake of phosphate has been known to induce renal tubular damage and interstitial inflammation, leading to acute kidney injury or chronic kidney disease in rodents and humans. However, sensitive and early biomarkers for phosphate‐induced kidney damage remain to be identified. Our previous RNA sequencing analysis of renal gene expression identified interleukin‐36α (IL‐36α) as a gene significantly upregulated by dietary phosphate load in mice. To determine the time course and dose dependency of renal IL‐36α expression induced by dietary phosphate load, we placed mice with or without uninephrectomy on a diet containing either 0.35%, 1.0%, 1.5%, or 2.0% inorganic phosphate for 10 days, 4 weeks, or 8 weeks and evaluated renal expression of IL‐36α and other markers of tubular damage and inflammation by quantitative RT‐PCR, immunoblot analysis, and immunohistochemistry. We found that IL‐36α expression was induced in distal convoluted tubules and correlated with phosphate excretion per nephron. The increase in IL‐36α expression was simultaneous with but more robust in amplitude than the increase in tubular damage markers such as Osteopontin and neutrophil gelatinase‐associated lipocalin, preceding the increase in expression of other inflammatory cytokines, including transforming growth factor‐α, interleukin‐1β, and transforming growth factor‐β1. We conclude that IL‐36α serves as a marker that reflects the degree of phosphate load excreted per nephron and of associated kidney damage.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐36α as a potential biomarker for renal tubular damage induced by dietary phosphate load

et al. 2020

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“…Interleukin-1 R3 is the co-receptor in three signaling pathways that involve six cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ). In vivo (animal models) targeting IL-1R3 significantly attenuated heterogeneous cytokine-driven inflammation and disease severity 58…”

Section: Understanding Better the Mechanisms Currently Targeted Withmentioning

confidence: 99%

Critical Points on the Use of Biologicals in Allergic Diseases and Asthma

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Cojanu

Laculiceanu

et al. 2020

Allergy Asthma Immunol Res

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Improved understanding of the contribution of immune-inflammatory mechanisms in allergic diseases and asthma has encouraged development of biologicals and small molecules specifically targeting the innate and adaptive immune response. There are several critical points impacting the efficacy of this stratified approach, from the complexity of disease endotypes to the effectiveness in real-world settings. We discuss here how these barriers can be overcome to facilitate the development of implementation science for allergic diseases and asthma.

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“…Lastly, IL1RAP (also named IL-1R3) blockade, using mAb81.2 and mAb3F8, which induces antibody-dependent cellular cytotoxicity and IL-1 signaling blockade in AML and CML cells provides evidence that IL1RAP may be a potent target in AML cells ( 33 , 193 ). All functions of the IL-1 family (IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ) are attenuated by IL1RAP blockade with the human IL1RAP antibody, MAB-hR3 ( 194 ). No increase in IL-6 production was observed, and IL1RAP blockade induced a broader anti-inflammatory activity than that associated with IL-1R1 blockade by IL-1Ra antagonist anakinra.…”

Section: Therapies In Developmentmentioning

confidence: 99%

Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics

et al. 2020

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Recent studies have provided several insights into acute myeloid leukemia. Studies based on molecular biology have identified eight functional mutations involved in leukemogenesis, including driver and passenger mutations. Insight into Leukemia stem cells (LSCs) and assessment of cell surface markers have enabled characterization of LSCs from hematopoietic stem and progenitor cells. Clonal evolution has been described as having an effect similar to that of microenvironment alterations. Such biological findings have enabled the development of new targeted drugs, including drug inhibitors and monoclonal antibodies with blockage functions. Some recently approved targeted drugs have resulted in new therapeutic strategies that enhance standard intensive chemotherapy regimens as well as supportive care regimens. Besides the progress made in adoptive immunotherapy, since allogenic hematopoietic stem cell transplantation enabled the development of new T-cell transfer therapies, such as chimeric antigen receptor T-cell and transgenic TCR T-cell engineering, new promising strategies that are investigated.

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IL-1R3 blockade broadly attenuates the functions of six members of the IL-1 family, revealing their contribution to models of disease

Cited by 61 publications

References 55 publications

Interleukin‐36α as a potential biomarker for renal tubular damage induced by dietary phosphate load

Interleukin‐36α as a potential biomarker for renal tubular damage induced by dietary phosphate load

Critical Points on the Use of Biologicals in Allergic Diseases and Asthma

Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics

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