IL-17C mediates the recruitment of tumor-associated neutrophils and lung tumor growth

Jungnickel, Christopher; Schmidt, LH; Bittigkoffer, L; Wiewrodt, Rainer; Wolf, Lisa; Wolf, Alexander; Menger, Michael D.; Bals, Robert; Beißwenger, Christoph

doi:10.1055/s-0037-1598418

Cited by 15 publications

(22 citation statements)

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“…This observation is in concordance with a report linking IL-17C to the recruitment of neutrophils in lung cancer. 18 Of note, IL-17C induced chemokines of Th1 (CXCL10), Th2 (CCL5) and Th17 immunity (CXCL8), thus pointing out that IL-17C is not exclusively related to one specific type of T cell-mediated inflammation. Recently it was shown that depletion of IL-17C signalling decreases inflammation in murine models of ISD.…”

Section: Discussionmentioning

confidence: 99%

IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema

Lauffer

Jargosch

Baghin

et al. 2020

Acad Dermatol Venereol

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Background Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL‐17C is an epithelial‐derived cytokine, whose impact on skin inflammation is unclear. Objective We sought to characterize the role of IL‐17C in human ISD. Methods IL‐17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT‐PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL‐17C was depleted using a new IL‐17C‐specific antibody (MOR106) in murine models of psoriasis (IL‐23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. Results Expression of IL‐17C mRNA and protein was elevated in various ISD. We demonstrate that IL‐17C potentiates the expression of innate cytokines, antimicrobial peptides (IL‐36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL‐17C in keratinocytes. Cell‐free supernatant of keratinocytes stimulated with IL‐17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL‐17C in immune cell recruitment. IL‐17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. Conclusion IL‐17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.

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Section: Discussionmentioning

confidence: 99%

IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema

Lauffer

Jargosch

Baghin

et al. 2020

Acad Dermatol Venereol

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“…Bronchoalveolar lavage (BAL) fluids were collected 24 h after the final OVA challenge as described before [18,21]. In brief, mice were euthanized, the tracheae were cannulated and BAL was performed with 1 ml of PBS flushed three times into the lungs.…”

Section: Bronchoalveolar Lavage and Cytokine Measurementsmentioning

confidence: 99%

“…Immunohistochemical staining was done as described before [17,21]. In brief, lungs were fixed by instillation of 4% formalin buffered in PBS under a constant hydrostatic pressure (30 cm H 2 O for 15 min), embedded in 1% agarose, cut into slices of exactly the same thickness, and embedded in paraffin.…”

Section: Lung Histologymentioning

confidence: 99%

“…Th17 cells, tissue resident T cells), whereas IL-17C is mainly of epithelial origin [8,9,[12][13][14]. In vitro and in vivo studies showed that the expression of IL-17C in airway epithelial cells is induced by lung pathogens including rhinoviruses and that IL-17C promotes the recruitment of neutrophils into the lung [12][13][14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

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The IL-17 receptor IL-17RE mediates polyIC-induced exacerbation of experimental allergic asthma

et al. 2020

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Background: The interleukin 17 receptor E (IL-17RE) is specific for the epithelial cytokine interleukin-17C (IL-17C). Asthma exacerbations are frequently caused by viral infections. Polyinosinic:polycytidylic acid (pIC) mimics viral infections through binding to pattern recognition receptors (e.g. TLR-3). We and others have shown that pIC induces the expression of IL-17C in airway epithelial cells. Using different mouse models, we aimed to investigate the function of IL-17RE in the development of experimental allergic asthma and acute exacerbation thereof. Methods: Wild-type (WT) and IL-17RE deficient (Il-17re −/−) mice were sensitized and challenged with OVA to induce allergic airway inflammation. pIC or PBS were applied intranasally when allergic airway inflammation had been established. Pulmonary expression of inflammatory mediators, numbers of inflammatory cells, and airway hyperresponsiveness (AHR) were analyzed. Results: Ablation of IL-17RE did not affect the development of OVA-induced allergic airway inflammation and AHR. pIC induced inflammation independent of IL-17RE in the absence of allergic airway inflammation. Treatment of mice with pIC exacerbated pulmonary inflammation in sensitized and OVA-challenged mice in an IL-17REdependent manner. The pIC-induced expression of cytokines (e.g. keratinocyte-derived chemokine (KC), granulocyte-colony stimulating factor (G-CSF)) and recruitment of neutrophils were decreased in Il-17re −/− mice. pIC-exacerbated AHR was partially decreased in Il-17re −/− mice. Conclusions: Our results indicate that IL-17RE mediates virus-triggered exacerbations but does not have a function in the development of allergic lung disease.

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“…Both IL-17A and C recruit CXCR2 + neutrophils to a variety of mucosal surfaces, organs and tumors by inducing the expression of CXCL1/2/5. 55,[59][60][61][62][63][64][65] In addition to ILC3s and T H 17 cells, innate lymphoid T cells may be a potent source of IL-17 at mucosal surfaces. 50,66,67 Neutrophils, in turn, control SFB levels as shown by the fact that SFB colonization of SFB negative Jackson mice is accelerated by the depletion of neutrophils with anti-Ly6G.…”

Section: Modulation Of Neutrophil Differentiation By the Microbiotamentioning

confidence: 99%

The interplay between neutrophils and microbiota in cancer

Smith

Trinchieri

2018

Journal of Leukocyte Biology

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The role of the microbiota in many diseases including cancer has gained increasing attention. Paired with this is our expanding appreciation for the heterogeneity of the neutrophil compartment regarding surface marker expression and functionality. In this review, we will discuss the influence of the microbiota on granulopoiesis and consequent activity of neutrophils in cancer. As evidence for this microbiota-neutrophil-cancer axis builds, it exposes new therapeutic targets to improve a cancer patient's outcome.

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IL-17C mediates the recruitment of tumor-associated neutrophils and lung tumor growth

Cited by 15 publications

References 0 publications

IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema

IL‐17C amplifies epithelial inflammation in human psoriasis and atopic eczema

The IL-17 receptor IL-17RE mediates polyIC-induced exacerbation of experimental allergic asthma

The interplay between neutrophils and microbiota in cancer

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