title: A mechanism for the induction of type 2 immune responses by a protease allergen in the genital tract.
abstract: 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.
authors.affiliation: Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Oh
authors.affiliation: Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.|Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Oh
authors.affiliation: Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.|Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Hi Eun
authors.initials: HE
authors.lastname: Jung
authors.affiliation: Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; heungkyu.lee@kaist.ac.kr.|Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
authors.forename: Heung Kyu
authors.identifier: 0000-0002-3977-1510
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000378:metabolism; D007114:Immunization / Q000379:methods*; D000067596:Interleukin-33 / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D010206:Papain / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014621:Vagina / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010206:Papain
keywords: IL-33; genital tract; papain; protease allergen; type 2 immunity