title: IL-33 is required for disposal of unnecessary cells during ovarian atresia through regulation of autophagy and macrophage migration.
abstract: Physiological processes such as ovarian follicle atresia generate large amounts of unnecessary cells or tissue detritus, which needs to be disposed of rapidly. IL-33 is a member of the IL-1 cytokine gene family. Constitutive expression of IL-33 in a wide range of tissues has hinted at its role beyond immune defense. We have previously reported a close correlation between IL-33 expression patterns and ovarian atresia. In this study, we demonstrated that IL-33 is required for disposal of degenerative tissue during ovarian atresia using Il33(-/-) mice. Deletion of the Il33 gene impaired normal disposal of atretic follicles, resulting in massive accumulations of tissue wastes abundant with aging-related catabolic wastes such as lipofuscin. Accumulation of tissue wastes in Il33(-/-) mice, in turn, accelerated ovarian aging and functional decline. Thus, their reproductive life span was shortened to two thirds of that for Il33(+/-) littermates. IL-33 orchestrated disposal mechanism through regulation of autophagy in degenerating tissues and macrophage migration into the tissues. Our study provides direct evidence supporting an expanded role of IL-33 in tissue integrity and aging through regulating disposal of unnecessary tissues or cells.
authors.affiliation: Department of Diagnostic Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX 77054;
authors.forename: Jean
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Diagnostic Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX 77054;
authors.forename: Colin
authors.initials: C
authors.lastname: Carlock
authors.affiliation: Department of Diagnostic Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX 77054;
authors.forename: Cindy
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030; and.
authors.forename: John
authors.initials: J
authors.lastname: Hicks
authors.affiliation: Department of Developmental Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030.
authors.forename: Henry P
authors.initials: HP
authors.lastname: Adams
authors.affiliation: Department of Diagnostic Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, TX 77054; yahuan.lou@uth.tmc.edu.
authors.forename: Yahuan
authors.initials: Y
authors.lastname: Lou
mesh_terms: D000818:Animals; D001343:Autophagy; D016922:Cellular Senescence / Q000276:immunology; D005260:Female; D005298:Fertility / Q000276:immunology*; D005496:Follicular Atresia / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D000067596:Interleukin-33; D007378:Interleukins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008062:Lipofuscin / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D008062:Lipofuscin