Universität zu Köln

Skuljec, Jelena ORCID: 0000-0001-8509-6563, Chmielewski, Markus, Happle, Christine, Habener, Anika, Busse, Mandy, Abken, Hinrich and Hansen, Gesine (2017). Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma. Front. Immunol., 8. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

Full text not available from this repository.

Abstract

Cellular therapy with chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg)-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR) and a chronic, T helper-2 (Th2) cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Skuljec, Jelena UNSPECIFIED orcid.org/0000-0001-8509-6563 UNSPECIFIED Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Happle, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Habener, Anika UNSPECIFIED UNSPECIFIED UNSPECIFIED Busse, Mandy UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Gesine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217811
DOI:	10.3389/fimmu.2017.01125
Journal or Publication Title:	Front. Immunol.
Volume:	8
Date:	2017
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CUTTING EDGE; BRONCHOALVEOLAR LAVAGE; MEDIATED SUPPRESSION; FOXP3 EXPRESSION; AUTOIMMUNE; STABILITY; COLITIS; PHENOTYPES; DISEASE Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21781