A mechanism for the induction of type 2 immune responses by a protease allergen in the genital tract

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The genital mucosa is a barrier that is constantly exposed to a variety of pathogens, allergens, and external stimuli. Although both allergen exposure and parasite infections frequently occur in the genital area, the mechanism by which immune responses-particularly type 2 immunity-are induced has rarely been studied in the genital mucosa. Here, we demonstrate the induction of T helper type 2 (Th2) immunity in the genital mucosa in response to a model allergen, the protease papain. Intravaginal papain immunization induced type 2 immunity in a manner that was dependent on protease activity and the estrous phase of the mice. In addition, IL-33 was released from the vaginal epithelia after intravaginal papain immunization, leading to the activation of type 2 innate lymphoid cells (ILC2s). Moreover, the IL-33-MyD88 (myeloid differentiation primary response gene 88) signaling pathway was critical for the induction of type 2 immunity. We also found that Th2 differentiation in response to intravaginal papain treatment requires a specific dendritic cell (DC) subset that is controlled by interferon regulatory factor 4 (IRF4). These findings suggest that type 2 immunity is induced by a unique mechanism in the genital tract, which is an important, but often overlooked, barrier surface.
Publisher
NATL ACAD SCIENCES
Issue Date
2017-02
Language
English
Article Type
Article
Keywords

SIMPLEX-VIRUS TYPE-2; INNATE LYMPHOID-CELLS; T-CELLS; DENDRITIC CELLS; IN-VIVO; RECURRENT VAGINITIS; MICE; IL-33; EOSINOPHILS; INFECTION

Citation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.114, no.7, pp.E1188 - E1195

ISSN
0027-8424
DOI
10.1073/pnas.1612997114
URI
http://hdl.handle.net/10203/222734
Appears in Collection
MSE-Journal Papers(저널논문)
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