We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Key Mechanism of Autoimmune and Inflammatory Diseases Revealed

By LabMedica International staff writers
Posted on 01 Feb 2018
Print article
Image: A diagram of structural activation of pro-inflammatory human cytokine IL-23 by cognate IL-23 receptor enables recruitment of the shared receptor IL-12Rβ1 (Photo courtesy of the University of Ghent).
Image: A diagram of structural activation of pro-inflammatory human cytokine IL-23 by cognate IL-23 receptor enables recruitment of the shared receptor IL-12Rβ1 (Photo courtesy of the University of Ghent).
The prevalence of psoriasis, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis, has been rapidly expanding over the last few decades. A crucial aspect of the molecular basis of these autoimmune and inflammatory has been unraveled.

For instance, an estimated 125 million people worldwide are affected by psoriasis and another 100 million by rheumatoid arthritis, while the presence of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) in ethnic populations and previously unaffected geographical regions is growing at alarming rates.

Interleukin-23 (IL-23), an IL-12 family cytokine, plays pivotal roles in pro-inflammatory T helper 17 cell responses linked to autoimmune and inflammatory diseases. Despite intense therapeutic targeting, structural and mechanistic insights into receptor complexes mediated by IL-23, and by IL-12 family members in general, have remained elusive. Scientists at the Flanders Institute for Biotechnology (VIB, Ghent, Belgium) and their colleagues discovered that the immunomodulatory cytokine IL-23 pro-inflammatory activity, which underlies a wide range of inflammatory diseases, critically depends on structural activation of the cytokine by its receptor, IL-23R.

The team determined a crystal structure of human IL-23 in complex with its cognate receptor, IL-23R, and revealed that IL-23R bound to IL-23 exclusively via its N-terminal immunoglobulin domain. The structural and functional hotspot of this interaction partially restructured the helical IL-23p19 subunit of IL-23 and restrained its IL-12p40 subunit to cooperatively bind the shared receptor IL-12Rβ1 with high affinity. Together with structural insights from the interaction of IL-23 with the inhibitory antibody briakinumab and by leveraging additional IL-23 antibody complexes, they proposed a mechanistic paradigm for IL-23 and IL-12 whereby cognate receptor binding to the helical cytokine subunits primes recruitment of the shared receptors via the IL-12p40 subunit.

Savvas Savvides, PhD, a professor and senior author of the study, said, “We were surprised to find that both IL-23 and its receptor change drastically to create an intimate cytokine-receptor interface. In this interface, the receptor uses a functional hotspot on IL-23, enabling it to recruit an essential co-receptor for pro-inflammatory signaling. The binding site of the co-receptor on IL-23 also emerged as an unexpected finding. What we have now discovered about the pro-inflammatory complex mediated by IL-23 appears to be a new paradigm in the field.” The study was published in the January 2018 issue of the journal Immunity.

Related Links:
Flanders Institute for Biotechnology

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
HLX
Complement 3 (C3) Test
GPP-100 C3 Kit
Gold Member
Real-time PCR System
GentierX3 Series

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The study showed the blood-based cancer screening test detects 83% of people with colorectal cancer with specificity of 90% (Photo courtesy of Guardant Health)

Blood Test Shows 83% Accuracy for Detecting Colorectal Cancer

Colorectal cancer is the second biggest cause of cancer deaths among adults in the U.S., with forecasts suggesting 53,010 people might die from it in 2024. While fewer older adults are dying from this... Read more

Hematology

view channel
Image: The Gazelle Hb Variant Test (Photo courtesy of Hemex Health)

First Affordable and Rapid Test for Beta Thalassemia Demonstrates 99% Diagnostic Accuracy

Hemoglobin disorders rank as some of the most prevalent monogenic diseases globally. Among various hemoglobin disorders, beta thalassemia, a hereditary blood disorder, affects about 1.5% of the world's... Read more

Microbiology

view channel
Image: The new platform is designed to perform blood-based diagnoses of nontuberculosis mycobacteria (Photo courtesy of 123RF)

New Blood Test Cuts Diagnosis Time for Nontuberculous Mycobacteria Infections from Months to Hours

Breathing in nontuberculous mycobacteria (NTM) is a common experience for many people. These bacteria are present in water systems, soil, and dust all over the world and usually don't cause any problems.... Read more

Industry

view channel
Image: These new assays are being developed for use on the recently introduced DxI 9000 Immunoassay Analyzer (Photo courtesy of Beckman Coulter)

Beckman Coulter and Fujirebio Expand Partnership on Neurodegenerative Disease Diagnostics

Beckman Coulter Diagnostics (Brea, CA, USA) and Fujirebio Diagnostics (Tokyo, Japan) have expanded their partnership focused on the development, manufacturing and clinical adoption of neurodegenerative... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.