title: A novel anti-IL4Rα nanoparticle efficiently controls lung inflammation during asthma.
abstract: Drug resistance and the harmful side effects accompanying the prolonged corticosteroid treatment of chronic pulmonary diseases prompted the development of more specific anti-inflammatory approaches. Several strategies aiming to block IL4Rα, the receptor for a key pro-inflammatory pathway, were investigated. However, their efficiency was limited, mostly due to the systemic or subcutaneous route of administrations. In this paper, we examined the ability of an intranasal treatment with biocompatible nanoparticles targeting IL4Rα to control lung inflammation in ovalbumin (OVA)-sensitized mice. OVA-sensitized mice were treated with anti-IL4Rα-conjugated nanoparticles. The levels of pro-inflammatory cytokines in the lungs and broncho-alveolar lavage fluid (BALF) were determined using a cytokine array assay. The effects of nanoparticle treatment on the activation of lung inflammatory cells and their ability to proliferate and produce cytokines were determined using fluorescence-activated cell sorting (FACS) analysis. Lung inflammation was also monitored using immunohistochemical staining. Treatment with the anti-IL4Rα nanoparticles significantly decreased pro-inflammatory cytokine expression and release in BALF and airway lung tissue in mice. The numbers of lung tissue lymphocytes, neutrophils and eosinophils were also decreased. Interestingly, anti-IL4Rα nanoparticles deactivated CD4 and CD8 T cells in lung tissue and inhibited their ability to produce pro-inflammatory cytokines to a significantly lower level than the treatment with free anti-IL4Rα. Moreover, they induced a sustained low level of lung inflammation for 1 week following the last instillation compared with the treatment with free anti-IL4Rα antibodies. Together, this data suggested that the enhanced tissue penetrability and sustainability of these nanoparticles improved the strength and durability of the immunosuppressive effects of anti-IL4Rα.
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Rabih
authors.identifier: 0000-0002-6516-7771
authors.initials: R
authors.lastname: Halwani
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.|Prince Naif Health Research Center, King Saud University Medical City, Riyadh, Saudi Arabia.
authors.forename: Asma
authors.initials: A
authors.lastname: Sultana Shaik
authors.affiliation: Jubail Industrial College, Department of Chemical and Process Engineering Technology, Jubail Industrial City, Saudi Arabia.
authors.forename: Elaref
authors.initials: E
authors.lastname: Ratemi
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Sibtain
authors.identifier: 0000-0002-9174-6590
authors.initials: S
authors.lastname: Afzal
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.|Prince Naif Health Research Center, King Saud University Medical City, Riyadh, Saudi Arabia.
authors.forename: Rosan
authors.initials: R
authors.lastname: Kenana
authors.affiliation: Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.affiliation: Department of Radiological Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Achraf
authors.initials: A
authors.lastname: Al Faraj
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D005260:Female; D018796:Immunoconjugates / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000276:immunology; D007167:Immunotherapy; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000627:therapeutic use*; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000276:immunology; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D016207:Cytokines; D018796:Immunoconjugates; D007073:Immunoglobulin E; D058726:Nanoconjugates; D010047:Ovalbumin; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit