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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 7; pp. E1188 - E1195
• Main Authors: Oh, Ji Eun, Oh, Dong Sun, Jung, Hi Eun, Lee, Heung Kyu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 14.02.2017
• Series: PNAS Plus
• Subjects: Allergies; Biological Sciences; Enzymes; Immune system; Pathogens; PNAS Plus; Urogenital system; genital tract; IL-33; papain; protease allergen; type 2 immunity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1612997114

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.