Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge.
IL-17 has been implicated in a number of inflammatory diseases, but the conditions of antigen exposure that drive the generation of Th17 responses have not been well defined. Epicutaneous (EC) immunization of mice with ovalbumin (OVA), which causes allergic skin inflammation with many characteristics of the skin lesions of atopic dermatitis, was found to also drive IL-17 expression in the skin. EC, but not i.p., immunization of mice with OVA drove the generation of IL-17-producing T cells in draining lymph nodes and spleen and increased serum IL-17 levels. OVA inhalation by EC-sensitized mice induced IL-17 and CXCL2 expression and neutrophil influx in the lung along with bronchial hyperreactivity, which were reversed by IL-17 blockade. Dendritic cells trafficking from skin to lymph nodes expressed more IL-23 and induced more IL-17 secretion by naïve T cells than splenic dendritic cells. This was inhibited by neutralizing IL-23 in vitro and by intradermal injection of anti-TGFbeta neutralizing antibody in vivo. Our findings suggest that initial cutaneous exposure to antigens in patients with atopic dermatitis may selectively induce the production of IL-17, which, in turn, drives inflammation of their airways.
He
Rui
R
Division of Immunology, Children's Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Oyoshi
Michiko K
MK
Jin
Haoli
H
Geha
Raif S
RS
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007114:Immunization; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D020381:Interleukin-17; D012333:RNA, Messenger; D010047:Ovalbumin