Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function. Chronic inflammation has been demonstrated to be the pathological basis of fibrosis. Emerging studies have revealed that most interleukin-17 (IL-17) isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity. Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes, including the initiation and exacerbation of IPF. Here, we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.

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Most cited references 81

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IL-17 and Th17 Cells.

Thomas Korn, Estelle Bettelli, Mohamed Oukka … (2009)

CD4+ T cells, upon activation and expansion, develop into different T helper cell subsets with different cytokine profiles and distinct effector functions. Until recently, T cells were divided into Th1 or Th2 cells, depending on the cytokines they produce. A third subset of IL-17-producing effector T helper cells, called Th17 cells, has now been discovered and characterized. Here, we summarize the current information on the differentiation and effector functions of the Th17 lineage. Th17 cells produce IL-17, IL-17F, and IL-22, thereby inducing a massive tissue reaction owing to the broad distribution of the IL-17 and IL-22 receptors. Th17 cells also secrete IL-21 to communicate with the cells of the immune system. The differentiation factors (TGF-beta plus IL-6 or IL-21), the growth and stabilization factor (IL-23), and the transcription factors (STAT3, RORgammat, and RORalpha) involved in the development of Th17 cells have just been identified. The participation of TGF-beta in the differentiation of Th17 cells places the Th17 lineage in close relationship with CD4+CD25+Foxp3+ regulatory T cells (Tregs), as TGF-beta also induces differentiation of naive T cells into Foxp3+ Tregs in the peripheral immune compartment. The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation. Furthermore, we now appreciate the importance of Th17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.

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The IL-17 Family of Cytokines in Health and Disease

Mandy McGeachy, Daniel Cua, Sarah Gaffen (2019)

The interleukin 17 (IL-17) family of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. IL-17A, the prototypical member of this family, just passed the 25 th anniversary of its discovery. While less is known about IL-17B-F, IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease. Over the past decade, however, it has become clear that the functions of IL-17 are far more nuanced than simply turning on inflammation. Accumulating evidence indicates that IL-17 has important context- and tissue-dependent roles in maintaining health during response to injury, physiological stress and infection. Here, we discuss the functions of the IL-17 family, with a focus on the balance between the pathogenic and protective roles of IL-17 in cancer and autoimmune disease, including results of therapeutic blockade and novel aspects of IL-17 signal transduction regulation. The IL-17 cytokine family is relatively poorly understood, apart from the prototypical, founding member, IL-17A, which has achieved notoriety for its role in autoimmunity. In this review, McGeachy, Cua and Gaffen discuss the pathogenic and protective roles of the IL-17 family in health, inflammation, injury, microbial regulation and cancer.

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Idiopathic pulmonary fibrosis

Annie Pardo, Ganesh Raghu, Luca Richeldi … (2017)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by progressive lung scarring and the histological picture of usual interstitial pneumonia (UIP). It is associated with increasing cough and dyspnoea and impaired quality of life. IPF affects ∼3 million people worldwide, with incidence increasing dramatically with age. The diagnostic approach includes the exclusion of other interstitial lung diseases or overlapping conditions and depends on the identification of the UIP pattern, usually with high-resolution CT; lung biopsy might be required in some patients. The UIP pattern is predominantly bilateral, peripheral and with a basal distribution of reticular changes associated with traction bronchiectasis and clusters of subpleural cystic airspaces. The biological processes underlying IPF are thought to reflect an aberrant reparative response to repetitive alveolar epithelial injury in a genetically susceptible ageing individual, although many questions remain on how to define susceptibility. Substantial progress has been made in the understanding of the clinical management of IPF, with the availability of two pharmacotherapeutic agents, pirfenidone and nintedanib, that decrease physiological progression and likely improve progression-free survival. Current efforts are directed at identifying IPF early, potentially relying on combinations of biomarkers that include circulating factors, demographics and imaging data.

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Author and article information

Contributors

Yun-Juan Nie: nieyunjuan@jiangnan.edu.cn

Shuo-Hua Wu: wushouhua0619@163.com

Ying-Hua Xuan: yhxuan@jiangnan.edu.cn

Gen Yan: gyan@stu.edu.cn

Journal

Journal ID (nlm-ta): Mil Med Res

Journal ID (iso-abbrev): Mil Med Res

Title: Military Medical Research

Publisher: BioMed Central (London )

ISSN (Print): 2095-7467

ISSN (Electronic): 2054-9369

Publication date (Electronic): 12 May 2022

Publication date PMC-release: 12 May 2022

Publication date Collection: 2022

Volume: 9

Electronic Location Identifier: 21

Affiliations

[1 ]GRID grid.258151.a, ISNI 0000 0001 0708 1323, Department of Basic Medicine, Wuxi School of Medicine, , Jiangnan University, ; Wuxi, 214000 Jiangsu China

[2 ]GRID grid.411679.c, ISNI 0000 0004 0605 3373, Department of Radiology, , The Second Affiliated Hospital, Medical College of Shantou University, ; Shantou, 515000 Shandong China

[3 ]Department of Basic Medicine, Xiamen Medical College, Xiamen, 361000 Fujian China

[4 ]Department of Radiology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, 361000 Fujian China

Article

Publisher ID: 382

DOI: 10.1186/s40779-022-00382-3

PMC ID: 9102601

PubMed ID: 35550651

SO-VID: 552b94ed-e0cd-4c84-8651-2c3f6c88b31d

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 8 October 2021

Date accepted : 12 April 2022

Funding

Funded by: the Joint Funds for the Health and Education of Fujian Province

Award ID: No. 2019-WJ- 31

Award Recipient : Gen Yan

Funded by: FundRef http://dx.doi.org/10.13039/501100002418, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College;

Award ID: No. HXJB-15

Award Recipient : Gen Yan

Funded by: FundRef http://dx.doi.org/10.13039/501100004608, Natural Science Foundation of Jiangsu Province;

Award ID: BK20180616

Award Recipient : Yun-Juan Nie

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Keywords: interleukin-17 (il-17) family,il-17 receptor,inflammation,idiopathic pulmonary fibrosis

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Keywords: interleukin-17 (il-17) family, il-17 receptor, inflammation, idiopathic pulmonary fibrosis

Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis

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Biomarkers for Inflammatory Lung Disease

Most cited references 81

IL-17 and Th17 Cells.

The IL-17 Family of Cytokines in Health and Disease

Idiopathic pulmonary fibrosis

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