Chitinase 3‐like 1 protein plays a critical role in respiratory syncytial virus‐induced airway inflammation

Kim, Min Jung; Shim, Doo Hee; Cha, Hye‐Ran; Moon, Kuk‐Young; Yang, Chang Mo; Hwang, Su Jin; Kim, Kyung Won; Park, Jeon Han; Lee, Chang-Min; Elias, Jack A.; Sohn, Myung Hyun; Lee, Jae Myun

doi:10.1111/all.13661

Cited by 32 publications

(25 citation statements)

References 46 publications

(42 reference statements)

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“…Regarding the relationship between CHI3L1 and M2 macrophages, CHI3L1 has been found to stimulate respiratory syncytial virus (RSV)‐induced airway inflammation, partly via M2 macrophage activation . Based on the findings of several in vitro studies, M2 macrophages have recently been subdivided into four subgroups: M2a, M2b, M2c and M2d .…”

Section: Discussionmentioning

confidence: 99%

Chitinase 3‐like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

Kwak

Hong

Kim

et al. 2019

Clin Experimental Allergy

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Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by defective skin barrier and Th2 immune responses. Chitinase 3‐like 1 (CHI3L1), also known as breast regression protein 39 (BRP‐39) in mice and human homologue YKL‐40, plays important roles in Th2 inflammation and allergen sensitization. CHI3L1 has been implicated in a variety of diseases including asthma characterized by inflammation, apoptosis and tissue remodelling, but its role in AD remains elusive. Objective The aim of this study was to investigate the role of CHI3L1 in the development and progression of AD. Results We investigated YKL‐40 levels in the serum and skin of AD patients by ELISA and immunofluorescence, respectively. Using a murine model of AD induced by ovalbumin (OVA), we investigated Th2 immune responses, M2 macrophage activation and skin barrier gene expression using wild‐type (WT) and BRP‐39 null mutant (BRP‐39−/−) mice. YKL‐40 level was significantly increased in serum of AD patients. In addition, both mRNA and protein expression levels of BRP‐39 were higher in OVA‐sensitized WT mice than in control mice. OVA‐sensitized BRP‐39−/− mice showed decreased epidermal thickness, lower total serum IgE, Th2 cytokine levels and CD4+ effector T cell populations than OVA‐sensitized WT mice. Induction of BRP‐39 was dominant in dermal macrophages. BRP‐39 deficiency was found to be involved in M2 macrophage activation. Consistently, the YKL‐40 level in the skin of AD patients was higher than in normal subjects and it was expressed in dermal macrophages. BRP‐39 deficiency attenuated dysregulation of skin barrier and tight junction genes. Conclusions and Clinical Relevance These findings demonstrate that CHI3L1 mediates the development of AD induced by OVA, affecting Th2 inflammation, M2 macrophage activation and skin barrier function.

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Section: Discussionmentioning

confidence: 99%

Chitinase 3‐like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

Kwak

Hong

Kim

et al. 2019

Clin Experimental Allergy

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“…Th2 cytokine levels and airway inflammation are known to be elevated in respiratory syncytial virus (RSV) infection but were reportedly diminished in the absence of CHI3L1. 43 In lung metastasis, CHI3L1 also plays a significant role in the pathogenesis of Th2 inflammation. CHI3L1 expression levels were found to be elevated in Th2 cells and CHI3L1-deficient T cells were prone to differentiate into Th1 cells as a result of increased interferon-gamma signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also indicated that CHI3L1 is involved in M2 macrophage polarization in atopic dermatitis and RSV infection. 19 43 This effect could be due to Th2 cytokines, such as IL-4 and IL-13, which are M2 polarization drivers. 45 Therefore, we suspect that increased expression of Th2 cytokines is involved in the development of the M2 phenotype, and that these synergistic effects may promote food allergy.…”

Section: Discussionmentioning

confidence: 99%

Chitinase 3-Like 1 Contributes to Food Allergy via M2 Macrophage Polarization

Kim

Hong

et al. 2020

Allergy Asthma Immunol Res

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Purpose Food allergy is a hypersensitive immune response to specific food proteins. Chitinase 3-like 1 (CHI3L1, also known as YKL-40 in humans or BRP-39 in mice) is associated with various chronic diseases, such as cancer, rheumatoid arthritis, and allergic disease. CHI3L1 is involved in allergen sensitization and type 2 helper T (Th2) inflammation, but the role of CHI3L1 in food allergy remains unclear. In this study, we sought to investigate the role of CHI3L1 in the development of food allergy. Methods We measured serum levels of CHI3L1 in food allergic patients. Food allergy was induced in wild-type (WT) and CHI3L1 null mutant (CHI3L1 −/− ) BALB/c mice with ovalbumin (OVA). We investigated Th2 immune responses, M2 macrophage polarization, and mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) signaling pathways, and also performed transcriptome analysis. Results Serum levels of CHI3L1 were significantly higher in children with food allergy compared with those in healthy controls. Furthermore, CHI3L1 expression levels were elevated in WT mice after OVA treatment. Food allergy symptoms, immunoglobulin E levels, Th2 cytokine production, and histological injury were attenuated in food allergy-induced CHI3L1 −/− mice compared with those in food allergy-induced WT mice. CHI3L1 expression was increased in OVA-treated WT intestinal macrophages and caused M2 macrophage polarization. Furthermore, CHI3L1 was involved in the extracellular signal-regulated kinases (ERK) and AKT signaling pathways and was associated with immune response and lipid metabolism as determined through transcriptome analysis. Conclusions CHI3L1 plays a pivotal role in Th2 inflammation and M2 macrophage polarization through MAPK/ERK and PI3K/AKT phosphorylation in food allergy.

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“…This usually occurs through mechanisms including upregulation of cell adhesion molecules, pathogen sensing receptors, and Toll-like receptors, which are common immunopathogenic factors mediating or involved in virus-and allergen-induced mucosal inflammation. [84][85][86][87][88][89][90][91] In addition, respiratory viruses were suggested to impact cilia and tight junction integrity in airway epithelial cells through the modulation of ZO-1, claudin-1, and occludin in the airway epithelial barrier, [92][93][94] which may be linked to pathophysiology of airway diseases. The nasal epithelium is the primary portal of entry for respiratory viruses and immediate target for viral replication in the airways.…”

Section: Respiratory Viral Infections and Allergymentioning

confidence: 99%

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Breiteneder

Diamant

Eiwegger

et al. 2019

Allergy

101

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This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractThe specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules.This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring Zuzana Diamanthttps://orcid.org/0000-0003-0133-0100Thomas Eiwegger https://orcid.org/0000-0002-2914-7829Wytske J. Fokkens https://orcid.org/0000-0003-4852-229X

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Chitinase 3‐like 1 protein plays a critical role in respiratory syncytial virus‐induced airway inflammation

Cited by 32 publications

References 46 publications

Chitinase 3‐like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

Chitinase 3‐like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation

Chitinase 3-Like 1 Contributes to Food Allergy via M2 Macrophage Polarization

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

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