Organizing structural principles of the IL-17 ligand–receptor axis

Wilson, Steven C; Caveney, Nathanael; Yen, Michelle; Pollmann, Christoph; Xiang, Xinyu; Jude, Kevin; Hafer, Maximillian; Tsutsumi, Naotaka; Piehler, Jacob; Garcia, K Christopher

doi:10.1038/s41586-022-05116-y

Cited by 31 publications

(18 citation statements)

References 57 publications

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“…The structure of VEGFR-1 in complex with VEGF- reveals how the full extracellular domains (ECDs) of the receptor dimers specifically recognize the VGEF-A cytokine. 42 Structures of IL-cytokines, including IL6, IL12/IL23 and IL17, bound to the receptors have been determined, 43 – 45 which reveal similarities and diversities in the coupling mechanisms of different IL family members. Also, chemokines activate the G protein-coupled receptors (GPCRs), which belong to the largest family of membrane proteins.…”

Section: Structural Studiesmentioning

confidence: 99%

Extracellular Vesicles (EVs) in Tumor Diagnosis and Therapy

Tan¹,

Wang

et al. 2023

Technol Cancer Res Treat

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In recent years, extracellular vesicles (EVs) have gained significant attention due to their tremendous potential for clinical applications. EVs play a crucial role in various aspects, including tumorigenesis, drug resistance, immune escape, and reconstruction of the tumor microenvironment. Despite the growing interest in EVs, many questions still need to be addressed before they can be practically applied in clinical settings. This paper aims to review EVs’ isolation methods, structure research, the roles of EVs in tumorigenesis and their mechanisms in multiple types of tumors, their potential application in drug delivery, and the expectations for their future in clinical research.

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Section: Structural Studiesmentioning

confidence: 99%

Extracellular Vesicles (EVs) in Tumor Diagnosis and Therapy

Tan¹,

Wang

et al. 2023

Technol Cancer Res Treat

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“…Recently, Wu et al confirmed that IL-25 binds to IL-17RB and identified 2 discrete linear and cyclic epitopes to be the primary docks [49]. Wilson et al further demonstrated that IL-25 only interacts with IL-17RB to allosterically facilitate the formation of the 'tip to tip' interface of IL-17RB-IL-17RA, which is a key receptor-receptor interaction required to initiate signal transduction [50]. Moreover, the study identified the IL-25-IL-17RB-IL-17RA ternary complex in which IL-25 forms a homodimer 2:2 complex with IL-17RB with two "wing-like" IL-17-RA co-receptors on both sides [50].…”

Section: Signal Transductionmentioning

confidence: 99%

“…Wilson et al further demonstrated that IL-25 only interacts with IL-17RB to allosterically facilitate the formation of the 'tip to tip' interface of IL-17RB-IL-17RA, which is a key receptor-receptor interaction required to initiate signal transduction [50]. Moreover, the study identified the IL-25-IL-17RB-IL-17RA ternary complex in which IL-25 forms a homodimer 2:2 complex with IL-17RB with two "wing-like" IL-17-RA co-receptors on both sides [50]. Due to this unique structure, both IL-17RB and IL-17RA are essential for IL-25 signal transduction.…”

Section: Signal Transductionmentioning

confidence: 99%

“…Due to this unique structure, both IL-17RB and IL-17RA are essential for IL-25 signal transduction. Competition between IL-25 and other IL-17 family members against collective receptors (IL-17RA and IL-17RB) may result in the disability of IL-25 [ 50 , 51 ]. Studies have shown that IL-25 inhibits IL-17 function as an IL-17A receptor antagonist in synoviocytes [ 52 ] and IL-25 function can also be inhibited by IL-17B in colon epithelial cells [ 51 ].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin 25 and its biological features and function in intestinal diseases

Jiang¹,

Wang²,

Zhang³

et al. 2022

cejoi

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Interleukin 25 (IL-25), also known as IL-17E, is a member of the IL-17 cytokine family and an important regulator of the type 2 immune response. Accumulating evidence suggests that IL-25 interacts with diverse immune as well as non-immune cells and plays a rather complicated role in different backgrounds of multiple organs. IL-25 has been studied in the physiology and pathology of the intestine to some extent. With epithelial cells being an important source in the intestine, IL-25 plays a key role in intestinal immune responses and is associated with inappropriate allergic reactions, autoimmune diseases, and cancer tumorigenesis. In this review, we discuss the emerging comprehension of the biology of IL-25, as well as its cellular sources, targets, and signaling transduction. In particular, we discuss how IL-25 participates in the development of intestinal diseases including helminth infection, inflammatory bowel diseases, food allergy and colorectal cancer, as well as its underlying role in future therapy.

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“…However, whether ICD was involved in the IIME remodeling of IC/BPS has never been reported yet, although various forms of RCD (such as apoptosis and pyroptosis) participated in the development of IC/BPS [ 9 , 10 ]. In addition, interleukin 17 (IL17) and interleukin 17 receptor A (IL17RA) are currently considered to be the important mediators of ICD [ 11 ], among which, IL17RA mediates the biological function of most IL17 family members [ 12 ]. The IL17 family has also been reported to play a key role in many IIME remodeling-associated diseases, such as psoriasis, yet the association between IL17RA and IC/BPS remains to be further clarified.…”

Section: Introductionmentioning

confidence: 99%

Immunogenic Cell Death Associated Molecular Patterns and the Dual Role of IL17RA in Interstitial Cystitis/Bladder Pain Syndrome

et al. 2023

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The unclear etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are responsible for the lack of effective treatment and the poor patient prognosis. Various studies show that chronic inflammation and immune responses are important factors contributing to the pathogenesis of IC/BPS. The process of immunogenic cell death (ICD) involves both the immune response and inflammatory process, and the involvement of ICD in IC/BPS pathogenesis has not been explored. Two IC/BPS transcriptome datasets collected from the Gene Expression Omnibus (GEO) database were used to identify distinct ICD-associated molecular patterns (IAMPs). IAMPs and IC/BPS subtypes were found to be related. The inflammatory immune microenvironments (IIME) in different IAMPs were studied. The potential mechanism by which the interleukin 17 receptor A (IL17RA) influences IC/BPS was examined using in vitro assays. The expression of ICD-related genes (IRGs) was upregulated in IC/BPS bladders, compared with normal bladders. Disease prediction models, based on differentially expressed IRGs, could accurately predict IC/BPS. The IC/BPS patients had two distinct IAMPs, each with its own subtype and clinical features and association with remodeling IIME. IL17RA, a well-established IC/BPS bladder biomarker, mediates both the inflammatory insult and the protective responses. In summary, the current study identified different IAMPs in IC/BPS, which may be involved in the pathogenesis of IC/BPS by remodeling the IIME. The chronic inflammatory process in IC/BPS may be prolonged by IL17RA, which could mediate both pro- and anti-inflammatory responses. The IL17RA-associated pathway may play a significant role in the development of IC/BPS and can be used as a therapeutic target.

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Organizing structural principles of the IL-17 ligand–receptor axis

Cited by 31 publications

References 57 publications

Extracellular Vesicles (EVs) in Tumor Diagnosis and Therapy

Extracellular Vesicles (EVs) in Tumor Diagnosis and Therapy

Interleukin 25 and its biological features and function in intestinal diseases

Immunogenic Cell Death Associated Molecular Patterns and the Dual Role of IL17RA in Interstitial Cystitis/Bladder Pain Syndrome

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