Dysregulation in lung immunity — The protective and pathologic Th17 response in infection

Way, Emily E.; Chen, Kong; Kolls, Jay K.

doi:10.1002/eji.201343713

Cited by 35 publications

(27 citation statements)

References 67 publications

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“…Airborne insults such like cigarette smoke, diesel dusts, bacterial infection and allergens induce the release of chemokines IL6, IL8, TNF, IL-1, GM-SCF, MCP-1 from airway epithelial cells [12, 20, 21, 29, 47, 58, 59, 68, 77, 98, 101, 115, 117, 119, 120, 143]. Release of these cytokines either recruit neutrophils directly [140] or induce IL-17 release from T H 17 cells [137]. The outcome of neutrophil enrichment is a cytokine profile, which is dominated by TNF-α, IL-1β, IL-6, IL-17, IL-18, IL-32 and TGF-β [14] (Fig.…”

Section: Tjs In Early Lung Inflammation Copd and Acute Lung Injurymentioning

confidence: 99%

Tight junctions in pulmonary epithelia during lung inflammation

Wittekindt

2016

Pflugers Arch - Eur J Physiol

174

131

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Inflammatory lung diseases like asthma bronchiale, chronic obstructive pulmonary disease and allergic airway inflammation are widespread public diseases that constitute an enormous burden to the health systems. Mainly classified as inflammatory diseases, the treatment focuses on strategies interfering with local inflammatory responses by the immune system. Inflammatory lung diseases predispose patients to severe lung failures like alveolar oedema, respiratory distress syndrome and acute lung injury. These life-threatening syndromes are caused by increased permeability of the alveolar and airway epithelium and exudate formation. However, the mechanism underlying epithelium barrier breakdown in the lung during inflammation is elusive. This review emphasises the role of the tight junction of the airway epithelium as the predominating structure conferring epithelial tightness and preventing exudate formation and the impact of inflammatory perturbations on their function.

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Section: Tjs In Early Lung Inflammation Copd and Acute Lung Injurymentioning

confidence: 99%

Tight junctions in pulmonary epithelia during lung inflammation

Wittekindt

2016

Pflugers Arch - Eur J Physiol

174

131

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“…Acidification of the airways in CF patients decreases antimicrobial protein function , providing an explanation for increased colonization by opportunistic pathogens. High bacteria burdens coupled with impaired antimicrobial activity may contribute to the pathological effects associated with IL‐17 in CF (reviewed in ).…”

Section: Pulmonary Epithelial Immune Barriersmentioning

confidence: 99%

Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense

McAleer

Kolls

2014

Immunological Reviews

Self Cite

173

141

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Summary Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments likely require manipulating the inflammatory response to pathogenic microbes or allergens. Here we review mechanisms controlling the production and functions of interleukin-17 (IL-17) and IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (γδT cells, natural killer cells, innate lymphoid cells) are the major source of IL-17 and IL-22 during acute infections, while CD4+ T-helper 17 (Th17) cells contribute to vaccine-induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T-cell activation. CD11b+ DCs stimulated with bacteria or fungi secrete IL-1β and IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL-1β and IL-23 release, increasing susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL-17 also contributes to anti-bacterial immunity, while IL-22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary inflammation.

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“…These two members share the highest degree of homology and show similar functions. Numerous studies have demonstrated that IL-17 and IL-17F are critical molecules in mucosal host defense and inflammatory diseases (Chen and Kolls, 2013; Kumar and Subramaniyam, 2015; Way et al, 2013). Infections and inflammatory diseases increase the accumulation of IL-17-producing cells in lung tissue.…”

Section: Introductionmentioning

confidence: 99%

IL-17 Receptor Signaling in the Lung Epithelium Is Required for Mucosal Chemokine Gradients and Pulmonary Host Defense against K. pneumoniae

Chen

Eddens

Trevejo-Nuñez

et al. 2016

Cell Host & Microbe

Self Cite

126

108

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Summary The cytokine IL17, and signaling via its heterodimeric IL-17RA/IL-17RC receptor, is critical for host defense against extracellular bacterial and fungal pathogens. Polarized lung epithelial cells express IL-17RA and IL-17RC basolaterally. However, their contribution to IL-17-dependent pulmonary defenses in vivo remains to be determined. To address this, we generated mice with conditional deletion of Il17ra or Il17rc in Scgb1a1-expressing club cells, a major component of the murine bronchiolar epithelium. These mice displayed an impaired ability to recruit neutrophils into the airway lumen in response to IL17, a defect in bacterial clearance upon mucosal challenge with the pulmonary pathogen Klebsiella pneumoniae, and substantially reduced epithelial expression of the chemokine Cxcl5. Neutrophil recruitment and bacterial clearance were restored by intranasal administration of recombinant CXCL5. Our data show that IL-17R signaling in the lung epithelium plays a critical role in establishing chemokine gradients that are essential for mucosal immunity against pulmonary bacterial pathogens.

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Dysregulation in lung immunity — The protective and pathologic Th17 response in infection

Cited by 35 publications

References 67 publications

Tight junctions in pulmonary epithelia during lung inflammation

Tight junctions in pulmonary epithelia during lung inflammation

Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense

IL-17 Receptor Signaling in the Lung Epithelium Is Required for Mucosal Chemokine Gradients and Pulmonary Host Defense against K. pneumoniae

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