Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model.
BACKGROUND
Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation.


METHODS
BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes.


RESULTS
The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung.


CONCLUSIONS
IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation.
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Hiroki
H
Tashiro
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Koichiro
K
Takahashi
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Shinichiro
S
Hayashi
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Go
G
Kato
Institute of Tokyo Environmental Allergy, Tokyo, Japan.
Keigo
K
Kurata
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Shinya
S
Kimura
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Naoko
N
Sueoka-Aragane
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000067596:Interleukin-33 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D047589:Leukocyte Reduction Procedures; D008081:Liposomes / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D039981:Pyroglyphidae / Q000737:chemistry / Q000276:immunology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D000950:Antigens, Ly; D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D008081:Liposomes; C494192:Ly-6C antigen, mouse; C442281:Mydgf protein, mouse; D004002:Clodronic Acid; D000094632:Thymic Stromal Lymphopoietin