IL-17a promotes sociability in mouse models of neurodevelopmental disorders

doi:10.1038/s41586-019-1843-6

GSTDTAP > 地球科学

DOI	10.1038/s41586-019-1843-6
	IL-17a promotes sociability in mouse models of neurodevelopmental disorders
	Reed, Michael Douglas 1,2; Yim, Yeong Shin 1,2; Wimmer, Ralf D.1,2,3; Kim, Hyunju 4; Ryu, Changhyeon 1,2; Welch, Gwyneth Margaret 1,2; Andina, Matias 1,2; King, Hunter Oren 2; Waisman, Ari 5; Halassa, Michael M.1,2,3; Huh, Jun R.4,6,7; Choi, Gloria B.1,2
	2020-05-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	577 期号:7789 页码:249-+
文章类型	Article
语种	英语
国家	USA; Germany
英文关键词	A subset of children with autism spectrum disorder appear to show an improvement in their behavioural symptoms during the course of a fever, a sign of systemic inflammation(1,2). Here we elucidate the molecular and neural mechanisms that underlie the beneficial effects of inflammation on social behaviour deficits in mice. We compared an environmental model of neurodevelopmental disorders in which mice were exposed to maternal immune activation (MIA) during embryogenesis(3,4) with mouse models that are genetically deficient for contactin-associated protein-like 2 (Cntnap2)(5), fragile X mental retardation-1 (Fmr1)(6) or Sh3 and multiple ankyrin repeat domains 3 (Shank3)(7). We establish that the social behaviour deficits in offspring exposed to MIA can be temporarily rescued by the inflammatory response elicited by the administration of lipopolysaccharide (LPS). This behavioural rescue was accompanied by a reduction in neuronal activity in the primary somatosensory cortex dysgranular zone (S1DZ), the hyperactivity of which was previously implicated in the manifestation of behavioural phenotypes associated with offspring exposed to MIA(8). By contrast, we did not observe an LPS-induced rescue of social deficits in the monogenic models. We demonstrate that the differences in responsiveness to the LPS treatment between the MIA and the monogenic models emerge from differences in the levels of cytokine production. LPS treatment in monogenic mutant mice did not induce amounts of interleukin-17a (IL-17a) comparable to those induced in MIA offspring bypassing this difference by directly delivering IL-17a into S1DZ was sufficient to promote sociability in monogenic mutant mice as well as in MIA offspring. Conversely, abrogating the expression of IL-17 receptor subunit a (IL-17Ra) in the neurons of the S1DZ eliminated the ability of LPS to reverse the sociability phenotypes in MIA offspring. Our data support a neuroimmune mechanism that underlies neurodevelopmental disorders in which the production of IL-17a during inflammation can ameliorate the expression of social behaviour deficits by directly affecting neuronal activity in the central nervous system.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000506682500043
WOS关键词	FEVER ; NEURONS ; ABNORMALITIES ; PHENOTYPES ; BEHAVIORS ; INFECTION ; CHILDREN ; CIRCUIT ; IMPROVE ; PATHWAY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281467
专题	地球科学资源环境科学气候变化
作者单位	1.MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA; 2.MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA; 3.MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA; 4.Harvard Med Sch, Dept Immunol, Blavatnik Inst, Boston, MA 02115 USA; 5.Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, Mainz, Germany; 6.Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA 02115 USA; 7.Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Reed, Michael Douglas,Yim, Yeong Shin,Wimmer, Ralf D.,et al. IL-17a promotes sociability in mouse models of neurodevelopmental disorders[J]. NATURE,2020,577(7789):249-+.
APA	Reed, Michael Douglas.,Yim, Yeong Shin.,Wimmer, Ralf D..,Kim, Hyunju.,Ryu, Changhyeon.,...&Choi, Gloria B..(2020).IL-17a promotes sociability in mouse models of neurodevelopmental disorders.NATURE,577(7789),249-+.
MLA	Reed, Michael Douglas,et al."IL-17a promotes sociability in mouse models of neurodevelopmental disorders".NATURE 577.7789(2020):249-+.