Il-10

Il-10
Name	Interleukin-10
Organism	Human
Uniprot	P22301
Gene	IL10
Length	178 aa
Location	Chromosome 1

Il-10

Introduction

Interleukin-10 is an anti-inflammatory cytokine produced by a variety of immune and non-immune cells. First characterized in studies of murine T helper cell regulation and macrophage suppression, it plays central roles in modulating responses in infection, autoimmunity, and tissue repair. Research on this cytokine has involved investigators and institutions such as Cytokine Research Laboratory, National Institutes of Health, Howard Hughes Medical Institute, University of Oxford, and Stanford University.

Structure and Biochemical Properties

The cytokine is a secreted homodimeric protein with each monomer comprising ~178 amino acids and a typical four-helix bundle fold common to the interleukin family. Structural analyses using techniques pioneered at European Molecular Biology Laboratory, Max Planck Institute, and MRC Laboratory of Molecular Biology revealed a compact dimer interface and receptor-binding surfaces. Crystallography and solution NMR studies performed in facilities including Diamond Light Source and Brookhaven National Laboratory mapped contact residues critical for interaction with the heterotetrameric receptor complex composed of subunits characterized by work at Salk Institute, Cold Spring Harbor Laboratory, and University of Cambridge. Post-translational modifications documented in proteomic studies were identified using mass spectrometry platforms at EMBL-EBI and Proteome Institute.

Gene and Expression

The IL10 gene is located on human chromosome 1 and its promoter contains regulatory elements that respond to signaling pathways characterized in studies at Yale University, Harvard Medical School, and University of California, San Francisco. Transcriptional control involves factors described in reports from National Cancer Institute, Max Planck Institute for Infection Biology, and Institut Pasteur, including promoter polymorphisms associated with differential expression in populations studied by groups at Johns Hopkins University and Karolinska Institutet. Expression is inducible in cell types identified by investigators at Imperial College London, Weizmann Institute of Science, and University of Tokyo, and is regulated by stimuli cataloged in experiments from Centers for Disease Control and Prevention, Walter Reed Army Institute of Research, and Peter Doherty Institute.

Biological Functions and Mechanisms

Interleukin-10 modulates immune signaling pathways by engaging a receptor complex that activates JAK-STAT signaling cascades elucidated in seminal work at University of California, Berkeley, Massachusetts Institute of Technology, and University of Pennsylvania. Downstream effects include transcriptional programs characterized in collaborations involving Broad Institute, European Bioinformatics Institute, and Dana-Farber Cancer Institute. Cellular sources and targets were mapped in lineage-tracing and flow cytometry studies at Fred Hutchinson Cancer Center, Karolinska University Hospital, and Cleveland Clinic. Functional roles in limiting inflammation and promoting resolution were demonstrated in in vivo models developed at Rothamsted Research, Rockefeller University, and University College London.

Role in Disease and Clinical Significance

Altered levels and genetic variants have been associated with infectious disease outcomes studied by researchers at World Health Organization, Global Fund, and Bill & Melinda Gates Foundation-supported programs. Associations with autoimmune disorders were reported in patient cohorts from Mayo Clinic, Mount Sinai Hospital, and University of Chicago Medical Center. Tumor microenvironment studies from Dana-Farber Cancer Institute, MD Anderson Cancer Center, and Institut Gustave Roussy highlighted immunosuppressive roles linked to prognosis in certain malignancies. Clinical correlations with transplant rejection, sepsis, and chronic inflammatory conditions were observed in multicenter trials coordinated by European Society of Clinical Microbiology and Infectious Diseases, American College of Rheumatology, and International Sepsis Forum.

Therapeutic Applications and Research

Therapeutic strategies explored include recombinant cytokine administration, gene therapy vectors developed at Genentech, Amgen, and Novartis, and biologics that modulate its pathway in preclinical programs run by Wellcome Trust, Pfizer, and Roche. Clinical trials testing recombinant cytokine or IL-10–based constructs were registered and conducted with participation from National Cancer Institute, European Medicines Agency, and industry partners such as GlaxoSmithKline. Biomarker studies using platforms from Abbott Laboratories, Roche Diagnostics, and Siemens Healthineers evaluated IL-10 levels for prognosis and stratification. Emerging approaches leverage synthetic biology groups at MIT Media Lab and ETH Zurich to produce engineered cells and vectors for controlled IL-10 delivery.

History of Discovery and Nomenclature

Initial functional descriptions emerged from murine studies of T helper cell differentiation conducted by research teams associated with National Institute of Allergy and Infectious Diseases, Pasteur Institute, and Imperial College laboratories. Early naming reflected its role as a cytokine that limited type 1 helper T cell responses, with iterative nomenclature adopted by committees at International Union of Immunological Societies, Human Genome Organisation, and editorial boards of journals such as Nature and Science. Subsequent molecular cloning, expression cloning, and protein characterization were published by groups at University of California, San Diego, University of North Carolina at Chapel Hill, and University of Glasgow.

Category:Cytokines