IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung.
Allergic asthma is a chronic inflammatory disorder of the airway associated with bronchial obstruction, airway hyper-reactivity (AHR), and mucus production. The epithelium may direct and propagate asthmatic-like responses. Central to this theory is the observation that viruses, air pollution, and allergens promote epithelial damage and trigger the generation of IL-25, IL-33, and TSLP via innate pathways such as TLRs and purinergic receptors. Similarly, engineered nanomaterials promote a Th2-associated pathophysiology. In this study, we tested the hypothesis that instillation of multi-walled carbon nanotubes (MWCNT) impair pulmonary function in C57Bl/6 mice due to the development of IL-33-dependent Th2-associated inflammation. MWCNT exposure resulted in elevated levels of IL-33 in the lavage fluid (likely originating from airway epithelial cells), enhanced AHR, eosinophil recruitment, and production of Th2-associated cytokines and chemokines. Moreover, these events were dependent on IL-13 signaling and the IL-33/ST2 axis, but independent of T and B cells. Finally, MWCNT exposure resulted in the recruitment of innate lymphoid cells. Collectively, our data suggest that MWCNT induce epithelial damage that results in release of IL-33, which in turn promotes innate lymphoid cell recruitment and the development of IL-13-dependent inflammatory response.
Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, The University of Montana, Missoula, MT 59812-1552, USA. celine.beamer@umontana.edu
Celine A
CA
Beamer
Teri A
TA
Girtsman
Benjamin P
BP
Seaver
Krissy J
KJ
Finsaas
Christopher T
CT
Migliaccio
Victoria K
VK
Perry
James B
JB
Rottman
Dirk E
DE
Smith
Andrij
A
Holian
D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D018398:Homeodomain Proteins; C506535:Il33 protein, mouse; D018793:Interleukin-13; D000067596:Interleukin-33; D007378:Interleukins; D037742:Nanotubes, Carbon; C064658:RAG-1 protein