IL-33 is required for disposal of unnecessary cells during ovarian atresia through regulation of autophagy and macrophage migration.
IL-33 is required for disposal of unnecessary cells during ovarian atresia through regulation of autophagy and macrophage migration.
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DOI：
10.4049/jimmunol.1402503
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发表时间：
2015-03-01
期刊：
影响因子：
--
通讯作者：
Lou Y
中科院分区：
文献类型：
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作者：
Wu J;Carlock C;Zhou C;Nakae S;Hicks J;Adams HP;Lou Y
生理过程如卵泡闭锁会产生大量不必要的细胞或组织碎屑，需要迅速处理。白细胞介素33（IL 33）是IL 1细胞因子基因家族的成员。IL 33在广泛组织中的连续性表达暗示了其作用超出免疫防御。我们以前曾报道IL 33表达模式与卵巢闭锁密切相关。在这里，我们使用IL 33 −/−小鼠证明了在卵巢闭锁期间需要IL 33来处理退行性组织。Il 33基因的缺失损害了闭锁卵泡的正常处理，导致大量组织废物的积累，这些废物富含与衰老相关的分解代谢废物，如脂褐素。在Il 33 −/−小鼠中，组织废物的积累反过来加速了卵巢老化和功能衰退。因此，它们的生殖寿命缩短到Il 33 +/−同窝出生的2/3。IL 33通过调节退化组织中的自噬和巨噬细胞向组织中的迁移来协调处置机制。我们的研究提供了直接证据，支持IL 33通过调节不必要的组织或细胞的处理在组织完整性和衰老中的作用扩大。
Physiological processes such as ovarian follicle atresia generate large amounts of unnecessary cells or tissue detritus, which needs to be disposed of rapidly. Interleukin33 (IL33) is a member of the IL1 cytokine gene family. Consecutive expression of IL33 in a wide range of tissues has hinted at its role beyond immune defense. We have previously reported a close correlation between IL33 expression patterns and ovarian atresia. Here, we demonstrated that IL33 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 lifespan was shortened to 2/3 of that for Il33+/− littermates. IL33 orchestrated disposal mechanism through regulation of autophagy in degenerating tissues and macrophage migration into the tissues. Our study provided direct evidence supporting an expanded role of IL33 in tissue integrity and aging through regulating disposal of unnecessary tissues or cells.