Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival - 19/04/17
Abstract |
Background |
Pentraxin 3 (PTX3) is a multifunctional molecule that plays a nonredundant role at the crossroads between pathogen clearance, innate immune system, matrix deposition, female fertility, and vascular biology. It is produced at sites of infection and inflammation by both structural and inflammatory cells. However, its role in allergen-induced inflammation remains to be tested.
Objective |
We sought to determine the effect of Ptx3 deletion on ovalbumin (OVA)–induced allergic inflammation in a murine model of asthma.
Methods |
Bronchoalveolar lavage fluid was collected from patients with severe asthma and healthy subjects, and the level of PTX3 was determined by using ELISA. Ptx3+/+ and Ptx3−/− mice were sensitized and challenged with OVA and bronchoalveolar lavage fluid, and the lungs were collected for assessing inflammation. Lung tissue inflammation and mucus production were assessed by means of flow cytometry and hematoxylin and eosin and periodic acid-Schiff staining, respectively. flexiVent was used to determine airway resistance to methacholine in these mice.
Results |
Here we report that mice with severe asthma and OVA-sensitized/challenged mice had increased PTX3 levels in the lungs compared with healthy control mice. Mice lacking PTX3 have exaggerated neutrophilic/eosinophilic lung inflammation, mucus production, and airway hyperresponsiveness in an experimental model of OVA-induced asthma. Furthermore, OVA-exposed lung Ptx3−/− CD4 T cells exhibit an increased production of IL-17A, an effect that is accompanied by an increased signal transducer and activator of transcription 3 phosphorylation, reduced IL-2 production, and enhanced activation and survival. Also, we observed an increase in numbers of IL-6– and IL-23–producing dendritic cells in OVA-exposed Ptx3−/− mice compared with those in wild-type control mice.
Conclusion |
Altogether, PTX3 deficiency results in augmented airway hyperresponsiveness, mucus production, and IL-17A–dominant pulmonary inflammation, suggesting a regulatory role of PTX3 in the development of allergic inflammation.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Pentraxin 3, allergic inflammation, CD4 T cells, IL-17A, IL-2, survival, B-cell lymphoma 2, signal transducer and activator of transcription 3, dendritic cells, IL-6
Abbreviations used : AHR, BALF, Bcl-2, CFSE, DC, H&E, MCh, MLN, OVA, PAS, PRR, PTX3, SARS, SNP, STAT3
Plan
| Support for this work was provided by the Children's Hospital Research Institute of Manitoba and Manitoba Health Research Council Research Chair (to A.S.G.), the Children's Hospital Research Institute of Manitoba postdoctoral award (to J.Z.), and the Canadian Institute of Health Research (CIHR; grant no. 115115 to A.S.G.). Ptx3−/− mice were created with the support of the Eunice Kennedy Shriver National Institute of Child Health and Human grant HD033438. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 3
P. 950 - mars 2017 Retour au numéro
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