Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses.
J Allergy Clin Immunol
; 139(1): 246-257.e4, 2017 01.
Article
in En
| MEDLINE
| ID: mdl-27315767
ABSTRACT
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Respiratory Hypersensitivity
/
Vehicle Emissions
/
Lymphocytes
/
Antigens, Dermatophagoides
/
Air Pollutants
/
Particulate Matter
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Allergy Clin Immunol
Year:
2017
Type:
Article
Affiliation country:
Belgium