Dysregulation of type 2 innate lymphoid cells and T

Autor: Katrien C, De Grove, Sharen, Provoost, Rudi W, Hendriks, Andrew N J, McKenzie, Leen J M, Seys, Smitha, Kumar, Tania, Maes, Guy G, Brusselle, Guy F, Joos
Rok vydání: 2015
Předmět:
MHCII
MHC class II
AHR
Airway hyperresponsiveness
Mice
Transgenic
GATA3 Transcription Factor
Adaptive Immunity
complex mixtures
Respiratory Hypersensitivity
BALF
Bronchoalveolar lavage fluid
Animals
Antigens
Dermatophagoides
Lymphocytes
HDM
House dust mite
Lung
house dust mite
TSLP
Thymic stromal lymphopoietin
Cells
Cultured
Vehicle Emissions
TH2 response
Air Pollutants
MLN
Mediastinal lymph node
respiratory system
asthma
Diesel exhaust particles
DC
Dendritic cell
Immunity
Innate
DEPs
Diesel exhaust particles
respiratory tract diseases
Mice
Inbred C57BL
TCR
T-cell receptor
RORα
RAR-related orphan receptor α
Cytokines
Mechanisms of Allergy and Clinical Immunology
Female
Particulate Matter
type 2 innate lymphoid cell
Lymph Nodes
Bronchoalveolar Lavage Fluid
ILC2
Type 2 innate lymphoid cell
Rag
Recombination-activating gene
WT
Wild type
Zdroj: The Journal of Allergy and Clinical Immunology
ISSN: 1097-6825
Popis: Background Although the prominent role of TH2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known. Objective We sought to investigate the relative contribution of ILC2 and adaptive TH2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Methods Wild-type, Gata-3+/nlslacZ (Gata-3–haploinsufficient), RAR-related orphan receptor α (RORα)fl/flIL7RCre (ILC2-deficient), and recombination-activating gene (Rag) 2−/− mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and TH2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Results Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and TH2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and TH2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2−/− mice. Conclusion These data indicate that dysregulation of ILC2s and TH2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure.
Graphical abstract
Databáze: OpenAIRE
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