title: Pentraxin 3 deletion aggravates allergic inflammation through a TH17-dominant phenotype and enhanced CD4 T-cell survival.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Jyoti
authors: J
authors: Balhara
authors: Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Lianyu
authors: L
authors: Shan
authors: Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Jingbo
authors: J
authors: Zhang
authors: Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Anik
authors: A
authors: Muhuri
authors: Department of Physiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Andrew J
authors: AJ
authors: Halayko
authors: Department of Pathology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Muhamad S
authors: MS
authors: Almiski
authors: Department of Medicine, University of Chicago, Chicago, Ill.
authors: Diana
authors: D
authors: Doeing
authors: Department of Medicine, University of Chicago, Chicago, Ill.
authors: John
authors: J
authors: McConville
authors: Department of Pathology & Immunology, Baylor College of Medicine, Houston, Tex.
authors: Martin M
authors: MM
authors: Matzuk
authors: Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: abdel.gounni@umanitoba.sca.
authors: Abdelilah S
authors: AS
authors: Gounni
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D002097:C-Reactive Protein / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000276:immunology*; D000099153:Pentraxins
chemical_list: D000485:Allergens; D002097:C-Reactive Protein; D016207:Cytokines; D010047:Ovalbumin; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
keywords: B-cell lymphoma 2; CD4 T cells; IL-17A; IL-2; IL-6; Pentraxin 3; allergic inflammation; dendritic cells; signal transducer and activator of transcription 3; survival