IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2.
IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2.
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DOI：
10.1016/j.cmet.2021.08.004
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发表时间：
2021-11-02
期刊：
影响因子：
29
通讯作者：
Dixit, Vishwa Deep
中科院分区：
文献类型：
--
作者：
Goldberg, Emily L.;Shchukina, Irina;Youm, Yun-Hee;Ryu, Seungjin;Tsusaka, Takeshi;Young, Kyrlia C.;Camell, Christina D.;Dlugos, Tamara;Artyomov, Maxim N.;Dixit, Vishwa Deep
衰老损害了整合的免疫代谢反应，这些反应已经进化到维持恒温动物的核心体温，以度过寒冷的压力，感染和饮食限制。脂肪组织炎症调节产热应激反应，但脂肪组织驻留细胞如何煽动老年人产热衰竭尚不清楚。在这里，我们定义了脂肪驻留免疫系统的改变，并确定2型先天淋巴细胞（ILC 2）在衰老中丢失。通过补充IL-33将老年小鼠中的ILC 2数量恢复到成年小鼠中观察到的水平，未能将老年小鼠从代谢障碍中拯救出来，并增加了冷诱导的致死率。转录组学分析揭示了老年ILC 2的内在缺陷，成年ILC 2的过继转移足以保护老年小鼠免受寒冷。因此，脂肪ILC 2在衰老过程中的功能缺陷驱动产热衰竭。Goldberg等人发现，脂肪驻留的ILC 2在衰老过程中受损，部分原因是其主要存活细胞因子IL-33的表达失调。老年ILC 2获得促炎和衰老样转录特征，这可能有助于增加老年ILC 2扩增小鼠的冷致死率。
Aging impairs the integrated immunometabolic responses, which have evolved to maintain core body temperature in homeotherms to survive cold stress, infections, and dietary restriction. Adipose tissue inflammation regulates the thermogenic stress response, but how adipose tissue-resident cells instigate thermogenic failure in the aged are unknown. Here, we define alterations in the adipose-resident immune system and identify that type 2 innate lymphoid cells (ILC2s) are lost in aging. Restoration of ILC2 numbers in aged mice to levels seen in adults through IL-33 supplementation failed to rescue old mice from metabolic impairment and increased cold-induced lethality. Transcriptomic analyses revealed intrinsic defects in aged ILC2, and adoptive transfer of adult ILC2s are sufficient to protect old mice against cold. Thus, the functional defects in adipose ILC2s during aging drive thermogenic failure. Goldberg et al. find that adipose-resident ILC2s become impaired during aging, in part through dysregulated expression of their primary survival cytokine, IL-33. Aged ILC2s obtain proinflammatory and senescence-like transcriptional signatures, and this might contribute to increased cold lethality in old mice with expanded aged ILC2s.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1038/s41577-019-0180-1
发表时间：
2019-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Goronzy JJ;Weyand CM
通讯作者：
Weyand CM
影响因子：
20.8
作者：
Goldberg, Emily L.;Shchukina, Irina;Asher, Jennifer L.;Sidorov, Sviatoslav;Artyomov, Maxim N.;Dixit, Vishwa Deep
通讯作者：
Dixit, Vishwa Deep
影响因子：
29
作者：
Kolodin D;van Panhuys N;Li C;Magnuson AM;Cipolletta D;Miller CM;Wagers A;Germain RN;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
29
作者：
Camell, Christina D.;Guenther, Patrick;Dixit, Vishwa Deep
通讯作者：
Dixit, Vishwa Deep