4.5 Review

Research Progress of Interleukin-27 in Inflammatory Bowel Disease

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Article Immunology

Interleukin-27-dependent transcriptome signatures during neonatal sepsis

Jessica M. Povroznik et al.

Summary: Human newborns have increased vulnerability and risk of mortality from infection due to differences in immune responses compared to adults. The immune suppressive cytokine, IL-27, is elevated in neonatal cells and tissues. In a mouse model, deficient IL-27 signaling results in reduced mortality and better control of bacteria with less inflammation. The absence of IL-27 signaling leads to differential gene expression associated with inflammation and cytokine signaling, particularly in macrophages.

FRONTIERS IN IMMUNOLOGY (2023)

Article Immunology

IL-27 induces an IFN-like signature in murine macrophages which in turn modulate colonic epithelium

Caroline Andrews et al.

Summary: Mucosal delivery of IL-27 has been shown to have therapeutic benefit in murine models of inflammatory bowel disease (IBD). However, murine colonoids and primary intact colonic crypts were unresponsive to IL-27 in vitro and lacked detectable IL-27 receptors. On the other hand, macrophages in inflamed colon tissue were responsive to IL-27 in vitro and had potent effects on colonic epithelium.

FRONTIERS IN IMMUNOLOGY (2023)

Article Multidisciplinary Sciences

Structural insights into the assembly of gp130 family cytokine signaling complexes

Yi Zhou et al.

Summary: This article presents the cryo-electron microscopy structures of five signaling complexes of the IL-6 family cytokines, revealing their assembly and molecular interactions. The structures provide insights for therapeutic targeting of gp130-mediated signaling.

SCIENCE ADVANCES (2023)

Article Microbiology

IL-27 Signaling Promotes Th1 Response by Downregulating IL-10 Production in DCs during Chlamydial Respiratory Infection

Jiajia Zeng et al.

Summary: IL-27/IL-27R signaling plays a protective role in Chlamydia trachomatis infection by promoting Th1 response and suppressing neutrophilic inflammation. IL-27 expression was observed in dendritic cells (DCs), and its signaling in DCs restricted the production of IL-10, thus supporting the Th1 response against chlamydial infection.

MICROORGANISMS (2023)

Review Immunology

Heterogeneity of ILC2s in the Intestine; Homeostasis and Pathology

Shogo Sunaga et al.

Summary: Group 2 innate lymphoid cells (ILC2s) are a novel subset of lymphocytes that lack antigen receptors. They play essential roles in maintaining tissue homeostasis and inducing local immune responses characterized by type 2 cytokines. ILC2s are distributed across various organs, including the intestine, where they are activated by luminal antigens and regulated by intestinal epithelial cells and neuronal systems. They contribute to epithelial barrier function, clearance of luminal antigens, tissue repair, inflammation, and tissue fibrosis. Recent studies have highlighted their involvement in inflammatory bowel diseases. Single-cell analysis techniques provide insights into ILC2 heterogeneity and their regulatory roles in different tissues.

FRONTIERS IN IMMUNOLOGY (2022)

Article Cell & Tissue Engineering

Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation

Yugo Morita et al.

Summary: IL-27 is found to be elevated in patients with S. aureus osteomyelitis, suggesting its pathogenic role in the disease. In animal experiments, exogenous IL-27 administration can ameliorate infection-related symptoms and regulate immune and bone cell functions, indicating its importance in the disease.

BONE RESEARCH (2022)

Article Cell Biology

Elevated Levels of IL-27 Are Associated with Disease Activity in Patients with Crohn's Disease

Xiufang Cui et al.

Summary: Immune disorders play a crucial role in the pathogenesis of Crohn's disease, with increased immune response of Th1 cells and related cytokines associated with disease onset. IL-27 levels in CD patients were significantly higher than in controls, especially during active stages. IL-27 levels correlated with disease activity indicators and may be involved in regulating Th17 cell differentiation in CD development.

MEDIATORS OF INFLAMMATION (2021)

Review Cell Biology

The Interleukins Orchestrate Mucosal Immune Responses to Salmonella Infection in the Intestine

Fu-Chen Huang

Summary: Salmonella infection induces immune responses involving innate and adaptive immunity, affecting various cell types like intestinal epithelial cells, neutrophils, macrophages, dendric cells, and lymphocytes. Different interleukins play diverse roles in the infection process, including anti-inflammatory, pro-inflammatory, and antimicrobial defense functions.
Article Immunology

Gut epithelial IL-27 confers intestinal immunity through the induction of intraepithelial lymphocytes

Chia-Hao Lin et al.

Summary: IL-27 produced by intestinal epithelial cells plays a crucial role in promoting a specific subset of intraepithelial lymphocytes, contributing to barrier immunity in the gut. Loss of IL-27 in IECs leads to a selective defect in certain IEL populations, resulting in elevated pathogen burden during parasitic infection. This suggests that IL-27 from different cell types plays distinct roles in maintaining intestinal homeostasis.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

Article Gastroenterology & Hepatology

IL-27 induces LL-37/CRAMP expression from intestinal epithelial cells: implications for immunotherapy of Clostridioides difficile infection

Banglao Xu et al.

Summary: IL-27 can be involved in host immunity against Clostridioides difficile infection by induction of LL-37/CRAMP. Therefore, the IL-27-LL-37 axis may be a valuable pathway in the development of immune-based therapy.

GUT MICROBES (2021)

Review Biochemistry & Molecular Biology

Ageing, metabolism and the intestine

Maja C. Funk et al.

EMBO REPORTS (2020)

Review Immunology

The role of IL-22 in intestinal health and disease

Mary E. Keir et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

Review Immunology

Functions and regulation of T cell-derived interleukin-10

Christian Neumann et al.

SEMINARS IN IMMUNOLOGY (2019)

Review Medicine, General & Internal

Mechanisms of Disease: Inflammatory Bowel Diseases

Guilherme Piovezani Ramos et al.

MAYO CLINIC PROCEEDINGS (2019)

Article Immunology

IL-27/IL-27 Receptor Signaling Provides Protection in Clostridium difficile-Induced Colitis

Lifang Wang et al.

JOURNAL OF INFECTIOUS DISEASES (2018)

Article Gastroenterology & Hepatology

Induction of PIR-A/B+ DCs in the in vitro inflammatory condition and their immunoregulatory function

Fumi Matsui et al.

JOURNAL OF GASTROENTEROLOGY (2018)

Article Multidisciplinary Sciences

Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis

Tingting Zheng et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Gastroenterology & Hepatology

Understanding and Preventing the Global Increase of Inflammatory Bowel Disease

Gilaad G. Kaplan et al.

GASTROENTEROLOGY (2017)

Article Immunology

Interleukin 27 is up-regulated in patients with active inflammatory bowel disease

Janette Furuzawa Carballeda et al.

IMMUNOLOGIC RESEARCH (2016)

Article Immunology

Protective role of Interleukin 27 (IL-27) gene polymorphisms in patients with ulcerative colitis

Jesus K. Yamamoto-Furusho et al.

IMMUNOLOGY LETTERS (2016)

Review Immunology

The Immunobiology of Interleukin-27

Hiroki Yoshida et al.

ANNUAL REVIEW OF IMMUNOLOGY VOL 33 (2015)

Review Pediatrics

Inflammatory Bowel Disease in Children and Adolescents

Michael J. Rosen et al.

JAMA PEDIATRICS (2015)

Article Gastroenterology & Hepatology

Resident Bacteria-Stimulated Interleukin-10-Secreting B Cells Ameliorate T-Cell-Mediated Colitis by Inducing T-Regulatory-1 Cells That Require Interleukin-27 Signaling

Yoshiyuki Mishima et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2015)

Article Gastroenterology & Hepatology

Oral Delivery of IL-27 Recombinant Bacteria Attenuates Immune Colitis in Mice

Miranda L. Hanson et al.

GASTROENTEROLOGY (2014)

Article Multidisciplinary Sciences

Recombinant p35 from Bacteria Can Form Interleukin (IL-)12, but Not IL-35

Samadhi Aparicio-Siegmund et al.

PLOS ONE (2014)

Review Gastroenterology & Hepatology

Increasing Incidence and Prevalence of the Inflammatory Bowel Diseases With Time, Based on Systematic Review

Natalie A. Molodecky et al.

GASTROENTEROLOGY (2012)

Review Immunology

Interleukin-27: Balancing Protective and Pathological Immunity

Christopher A. Hunter et al.

IMMUNITY (2012)

Article Gastroenterology & Hepatology

Treatment with IL-27 attenuates experimental colitis through the suppression of the development of IL-17-producing T helper cells

Tetsumasa Sasaoka et al.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2011)

Article Medicine, Research & Experimental

Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling

Simon A. Jones et al.

JOURNAL OF CLINICAL INVESTIGATION (2011)

Article Immunology

IL-27 promotes T cell-dependent colitis through multiple mechanisms

Jennifer H. Cox et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2011)

Article Multidisciplinary Sciences

IL-27 structural analysis demonstrates similarities with ciliary neurotrophic factor (CNTF) and leads to the identification of antagonistic variants

Francois Rousseau et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Immunology

Interleukin-27 as a Negative Regulator of Human Neutrophil Function

J. P. Li et al.

SCANDINAVIAN JOURNAL OF IMMUNOLOGY (2010)

Article Gastroenterology & Hepatology

Interleukin-27 polymorphisms are associated with inflammatory bowel diseases in a Korean population

Chun-Shi Li et al.

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY (2009)

Article Genetics & Heredity

Common variants at five new loci associated with early-onset inflammatory bowel disease

Marcin Imielinski et al.

NATURE GENETICS (2009)

Review Medicine, General & Internal

MECHANISMS OF DISEASE Inflammatory Bowel Disease

Clara Abraham et al.

NEW ENGLAND JOURNAL OF MEDICINE (2009)

Review Immunology

Advances in understanding the anti-inflammatory properties of IL-27

J. S. Stumhofer et al.

IMMUNOLOGY LETTERS (2008)

Article Multidisciplinary Sciences

The inhibitory cytokine IL-35 contributes to regulatory T-cell function

Lauren W. Collison et al.

NATURE (2007)

Article Cell Biology

IFN-α regulates Toll-like receptor-mediated IL-27 gene expression in human macrophages

Jaana Pirhonen et al.

JOURNAL OF LEUKOCYTE BIOLOGY (2007)

Review Multidisciplinary Sciences

Unravelling the pathogenesis of inflammatory bowel disease

R. J. Xavier et al.

NATURE (2007)

Article Biochemistry & Molecular Biology

TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1

Ahjoku Amadi-Obi et al.

NATURE MEDICINE (2007)

Article Immunology

Protection from lethal septic peritonitis by neutralizing the biological function of interleukin 27

Stefan Wirtz et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2006)

Article Gastroenterology & Hepatology

Muc2-deficient mice spontaneously develop colitis, indicating that Muc2 is critical for colonic protection

Maria Van der Sluis et al.

GASTROENTEROLOGY (2006)

Review Gastroenterology & Hepatology

Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis

RB Sartor

NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY (2006)

Article Gastroenterology & Hepatology

T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis

K Honda et al.

INFLAMMATORY BOWEL DISEASES (2005)

Article Biochemistry & Molecular Biology

No inhibition of IL-27 signaling by soluble gp130

J Scheller et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2005)

Article Immunology

WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27

S Pflanz et al.

JOURNAL OF IMMUNOLOGY (2004)

Review Biochemistry & Molecular Biology

Principles of interleukin (IL)-6-type cytokine signalling and its regulation

PC Heinrich et al.

BIOCHEMICAL JOURNAL (2003)

Article Multidisciplinary Sciences

An important regulatory role for CD4+CD8αα T cells in the intestinal epithelial layer in the prevention of inflammatory bowel disease

G Das et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

Article Pediatrics

Presenting features of inflammatory bowel disease in Great Britain and Ireland

A Sawczenko et al.

ARCHIVES OF DISEASE IN CHILDHOOD (2003)