scholarly journals Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3000
Author(s):  
Milena Iwaszko ◽  
Sylwia Biały ◽  
Katarzyna Bogunia-Kubik
Keyword(s):  
Inflammatory Arthritis ◽  
Current Knowledge ◽  
Allergic Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
T Helper ◽  
T Helper 2 ◽  
Th2 Cytokine ◽  
Inflammatory Processes

Interleukin (IL)-4 and IL-13 belong to the T helper 2 (Th2) cytokine family, along with IL-3, IL-5, and IL-9. These cytokines are key mediators of allergic inflammation. They have important immunomodulatory activities and exert influence on a wide variety of immune cells, such as B cells, eosinophils, basophils, monocytes, fibroblasts, endothelial cells, airway epithelial cells, smooth muscle cells, and keratinocytes. Recent studies have implicated IL-4 and IL-13 in the development of various autoimmune diseases. Additionally, these cytokines have emerged as potential players in pathogenesis of inflammatory arthritis. Recent findings suggest that the IL-4 and IL-13 might play a significant role in the downregulation of inflammatory processes underlying RA pathology, and beneficially modulate the course of the disease. This review summarizes the biological features of the IL-4 and IL-13 and provides current knowledge regarding the role of these cytokines in inflammatory arthritis.

scholarly journals Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production

2020 ◽  
Vol 134 (13) ◽  
pp. 1735-1749 ◽  
Author(s):  
Lin Yuan ◽  
Xun Zhang ◽  
Ming Yang ◽  
Xizi Du ◽  
Leyuan Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Allergic Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Th2 Response ◽  
Integrin Β4 ◽  
Dust Mite ◽  
Asthma Patients ◽  
Deficient Mice

Abstract Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.

scholarly journals Interleukin-31 promotes fibrosis and T helper 2 polarization in systemic sclerosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai Kuzumi ◽  
Ayumi Yoshizaki ◽  
Kazuki M. Matsuda ◽  
Hirohito Kotani ◽  
Yuta Norimatsu ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Immune Responses ◽  
Dermal Fibroblasts ◽  
T Helper ◽  
Multisystem Disorder ◽  
Exact Role ◽  
T Helper 2 ◽  
Th2 Cytokine ◽  
Th2 Polarization

AbstractSystemic sclerosis (SSc) is a chronic multisystem disorder characterized by fibrosis and autoimmunity. Interleukin (IL)-31 has been implicated in fibrosis and T helper (Th) 2 immune responses, both of which are characteristics of SSc. The exact role of IL-31 in SSc pathogenesis is unclear. Here we show the overexpression of IL-31 and IL-31 receptor A (IL-31RA) in dermal fibroblasts (DFs) from SSc patients. We elucidate the dual role of IL-31 in SSc, where IL-31 directly promotes collagen production in DFs and indirectly enhances Th2 immune responses by increasing pro-Th2 cytokine expression in DFs. Furthermore, blockade of IL-31 with anti-IL-31RA antibody significantly ameliorates fibrosis and Th2 polarization in a mouse model of SSc. Therefore, in addition to defining IL-31 as a mediator of fibrosis and Th2 immune responses in SSc, our study provides a rationale for targeting the IL-31/IL-31RA axis in the treatment of SSc.

Role of CD4+CD25+Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways

2001 ◽  
Vol 164 (4) ◽  
pp. 680-687 ◽  
Author(s):  
AKIRA SUTO ◽  
HIROSHI NAKAJIMA ◽  
SHIN-ICHIRO KAGAMI ◽  
KOTARO SUZUKI ◽  
YASUSHI SAITO ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Allergic Inflammation ◽  
T Helper ◽  
T Helper 2

scholarly journals Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ian T. Stancil ◽  
Jacob E. Michalski ◽  
Duncan Davis-Hall ◽  
Hong Wei Chu ◽  
Jin-Ah Park ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Airway Epithelium ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
Chronic Lung Diseases ◽  
Distal Airway ◽  
Signaling Axis

AbstractThe airway epithelium serves as the interface between the host and external environment. In many chronic lung diseases, the airway is the site of substantial remodeling after injury. While, idiopathic pulmonary fibrosis (IPF) has traditionally been considered a disease of the alveolus and lung matrix, the dominant environmental (cigarette smoking) and genetic (gain of function MUC5B promoter variant) risk factor primarily affect the distal airway epithelium. Moreover, airway-specific pathogenic features of IPF include bronchiolization of the distal airspace with abnormal airway cell-types and honeycomb cystic terminal airway-like structures with concurrent loss of terminal bronchioles in regions of minimal fibrosis. However, the pathogenic role of the airway epithelium in IPF is unknown. Combining biophysical, genetic, and signaling analyses of primary airway epithelial cells, we demonstrate that healthy and IPF airway epithelia are biophysically distinct, identifying pathologic activation of the ERBB-YAP axis as a specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia. Furthermore, we demonstrate that this biophysical state and signaling axis correlates with epithelial-driven activation of the underlying mesenchyme. Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression.

Role of size and composition of traffic and agricultural aerosols in the molecular responses triggered in airway epithelial cells

2011 ◽  
Vol 23 (11) ◽  
pp. 627-640 ◽  
Author(s):  
Val Stéphanie ◽  
Martinon Laurent ◽  
Cachier Hélène ◽  
Yahyaoui Abderrazak ◽  
Marfaing Hélène ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Molecular Responses

scholarly journals Pharmacological Rationale for Targeting IL-17 in Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Experimental Models ◽  
Airflow Limitation ◽  
Interleukin 17 ◽  
Asthma Phenotype ◽  
T Helper 2 ◽  
Bronchial Biopsies

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

scholarly journals The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 360
Author(s):  
Janina Treffon ◽  
Sarah Ann Fotiadis ◽  
Sarah van Alen ◽  
Karsten Becker ◽  
Barbara C. Kahl
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Airway Epithelial Cells ◽  
Farm Animals ◽  
Airway Epithelial ◽  
Methicillin Resistant ◽  
Virulence Potential ◽  
Airway Infections ◽  
Severe Infections

Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S. aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF.

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