Allergy Asthma Immunol Res.  2018 Jul;10(4):406-419. 10.4168/aair.2018.10.4.406.

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

Affiliations
  • 1Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil. milena@bahia.fiocruz.br
  • 2Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
  • 3Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
  • 4Hospital Universitário Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.
  • 5Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Salvador, Bahia, Brazil.
  • 6Department of Diagnostics and Biomedical Sciences at The University of Texas Health Science Center, Houston, USA.
  • 7Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

Abstract

PURPOSE
The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract.
METHODS
Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis.
RESULTS
Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs.
CONCLUSIONS
Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.

Keyword

Dendritic cells; asthma; allergens, house dust mites; immunotherapy and tolerance induction

MeSH Terms

Administration, Intranasal
Animals
Antibodies
Antigens, Dermatophagoides
Asthma
Bronchoalveolar Lavage Fluid
Dendritic Cells*
Dexamethasone
Dust*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Gene Expression
Granulocyte-Macrophage Colony-Stimulating Factor
Hypersensitivity
Immunoglobulin E
Immunoglobulins
In Vitro Techniques
Inflammation*
Interleukin-4
Interleukins
Lung
Major Histocompatibility Complex
Mice
Mites*
Mucus
Spleen
T-Lymphocytes, Regulatory
Up-Regulation
Antibodies
Antigens, Dermatophagoides
Dexamethasone
Dust
Granulocyte-Macrophage Colony-Stimulating Factor
Immunoglobulin E
Immunoglobulins
Interleukin-4
Interleukins
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