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

Abstract

PurposeThe 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.MethodsMouse 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.ResultsInduction 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.ConclusionsPreventive 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.

Allergen Immunotherapy in Children User’s Guide

“…Monocyte‐derived tDCs of healthy individuals were demonstrated to favor differentiation of allergen‐specific Treg cells and in turn suppress T‐cell responses. In mouse models, tDCs were revealed to inhibit allergic airway inflammation . Better understanding of DCs with tolerogenic properties may contribute to the development of new therapy regimens, not only in allergy and asthma, but also autoimmunity and organ transplantation.…”

Tolerogenic Dendritic Cells Reduce Cardiac Inflammation and Fibrosis in Chronic Chagas Disease

“…This effect is probably caused by the immunosuppressive profile of tolerogenic dendritic cells, which have low immunostimulatory capacity, but with potential of inducing Treg cells via IL-10 secretion. As shown by recent studies, tolerogenic dendritic cells producing IL-10 induce tolerance via activation of Treg cells in murine models of autoimmune disease (22,34,35). Interestingly, in the absence of DCs, IL-10 is a cytokine which alone can induce FoxP3 expression and Treg differentiation (42).…”

“…The protocol used to produce dendritic cells (DCs) was adapted from a previously described methodology (22). Bone marrow from C57BL/6 mice was collected by flushing the femurs with RPMI medium (Sigma-Aldrich).…”

“…Considering the role of DCs in both the induction of adaptative immunity and in maintaining immunological tolerance, much attention has been given to the role of these cells in stimulating or preventing autoimmune diseases, associating the potential application of DCs as regulators for treatments of autoimmune diseases. Thus, tolerogenic dendritic cells (tDCs) are a promising therapeutic tool to reduce or prevent autoimmune diseases, including systemic lupus erythematosus (20), atherosclerosis (21), asthma allergic (22), rheumatoid, and inflammatory arthritis (23), experimental autoimmune myocarditis (24), myocardial infarction (25), immunotherapy of cancer (26), and solid organ transplantation (19).…”

Lipopolysaccharide-activated bone marrow-derived dendritic cells suppress ovalbumin(OVA)-induced asthma by ameliorating the immune microenvironment

“…Nevertheless, DCs may present distinct phenotypic and functional characteristics according to the stimulus that they received. Ample evidence has demonstrated that DCs differentiated under certain conditions are capable of inducing immune tolerance in multiple disease models ranging from autoimmune to allergic diseases [3][4][5][6][7] . These specific tolDCs are distinguished by the decreased expression of costimulatory molecules and proinflammatory cytokines along with enhancement of anti-inflammatory cytokines, thus leading to T cell anergy and Treg activation 8 .…”