Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells
Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii, a parasite that infects approximately two billion people, t...
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| Veröffentlicht in: | Nature neuroscience 2021-06, Vol.24 (6), p.818 |
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| creator | Xu, Zhipeng Zhang, Xiaoyun Chang, Hao Kong, Yue Ni, Yangyue Liu, Ran Zhang, Xiaolin Hu, Yang Yang, Zhi Hou, Min Mao, Rui Liu, Wen-Tao Du, Yasong Yu, Shunying Wang, Zhen Ji, Minjun Zhou, Zikai |
| description | Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii, a parasite that infects approximately two billion people, to induce MIA in mice. The adult male offspring showed autism-relevant behaviors and abnormal brain microstructure, along with a pro-inflammatory T-cell immune profile in the periphery and upregulation of interleukin-6 in brain astrocytes. We show that adoptive transfer of regulatory T (T
) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T
cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T
cells that constitute 32.6% of the pathogen-activated maternal T
population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T
cell transfer in neuropsychiatric disorders associated with immune alterations. |
| doi_str_mv | 10.1038/s41593-021-00837-1 |
| format | Article |
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) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T
cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T
cells that constitute 32.6% of the pathogen-activated maternal T
population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T
cell transfer in neuropsychiatric disorders associated with immune alterations.</description><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/s41593-021-00837-1</identifier><identifier>PMID: 33859437</identifier><language>eng</language><publisher>United States</publisher><subject>Adoptive Transfer - methods ; Animals ; Antigens, Protozoan - administration & dosage ; Antigens, Protozoan - toxicity ; Female ; HeLa Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Pregnancy ; Prenatal Exposure Delayed Effects - immunology ; Prenatal Exposure Delayed Effects - parasitology ; Social Interaction ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - parasitology ; Vocalization, Animal - physiology</subject><ispartof>Nature neuroscience, 2021-06, Vol.24 (6), p.818</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-0293-0255 ; 0000-0002-8853-5303 ; 0000-0002-4577-9826</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33859437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Zhipeng</creatorcontrib><creatorcontrib>Zhang, Xiaoyun</creatorcontrib><creatorcontrib>Chang, Hao</creatorcontrib><creatorcontrib>Kong, Yue</creatorcontrib><creatorcontrib>Ni, Yangyue</creatorcontrib><creatorcontrib>Liu, Ran</creatorcontrib><creatorcontrib>Zhang, Xiaolin</creatorcontrib><creatorcontrib>Hu, Yang</creatorcontrib><creatorcontrib>Yang, Zhi</creatorcontrib><creatorcontrib>Hou, Min</creatorcontrib><creatorcontrib>Mao, Rui</creatorcontrib><creatorcontrib>Liu, Wen-Tao</creatorcontrib><creatorcontrib>Du, Yasong</creatorcontrib><creatorcontrib>Yu, Shunying</creatorcontrib><creatorcontrib>Wang, Zhen</creatorcontrib><creatorcontrib>Ji, Minjun</creatorcontrib><creatorcontrib>Zhou, Zikai</creatorcontrib><title>Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><description>Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii, a parasite that infects approximately two billion people, to induce MIA in mice. The adult male offspring showed autism-relevant behaviors and abnormal brain microstructure, along with a pro-inflammatory T-cell immune profile in the periphery and upregulation of interleukin-6 in brain astrocytes. We show that adoptive transfer of regulatory T (T
) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T
cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T
cells that constitute 32.6% of the pathogen-activated maternal T
population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T
cell transfer in neuropsychiatric disorders associated with immune alterations.</description><subject>Adoptive Transfer - methods</subject><subject>Animals</subject><subject>Antigens, Protozoan - administration & dosage</subject><subject>Antigens, Protozoan - toxicity</subject><subject>Female</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Pregnancy</subject><subject>Prenatal Exposure Delayed Effects - immunology</subject><subject>Prenatal Exposure Delayed Effects - parasitology</subject><subject>Social Interaction</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - parasitology</subject><subject>Vocalization, Animal - physiology</subject><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtKAzEYhYMgtlZfwIXkBaLJ5DazlOINCoLUdckkf9rIJDNMMoU-gm9ti5fV2Xx853AQumH0jlFe32fBZMMJrRihtOaasDM0Z1IownSlZugy509KqZZ1c4FmnNeyEVzP0dc7ZDsB7j2OpsCYTIdDjFMCbGwJe1NCn0hIbrLgcAs7sw_9eIRMm_oxmi6UABmHhI2buoJjP-WTzedhDGmL2wMeTNn1W0jkV3j0_Fet8QhbbKHr8hU696bLcP2bC_Tx9LhevpDV2_Pr8mFFBkbrQiqplWXCKya0A1nJ1mnuGxCCKlEpLrUBqJ1tvOGt1safMG-1o7rh4BVfoNsf7zC1EdzmuDOa8bD5-4R_A28VZhU</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Xu, Zhipeng</creator><creator>Zhang, Xiaoyun</creator><creator>Chang, Hao</creator><creator>Kong, Yue</creator><creator>Ni, Yangyue</creator><creator>Liu, Ran</creator><creator>Zhang, Xiaolin</creator><creator>Hu, Yang</creator><creator>Yang, Zhi</creator><creator>Hou, Min</creator><creator>Mao, Rui</creator><creator>Liu, Wen-Tao</creator><creator>Du, Yasong</creator><creator>Yu, Shunying</creator><creator>Wang, Zhen</creator><creator>Ji, Minjun</creator><creator>Zhou, Zikai</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><orcidid>https://orcid.org/0000-0003-0293-0255</orcidid><orcidid>https://orcid.org/0000-0002-8853-5303</orcidid><orcidid>https://orcid.org/0000-0002-4577-9826</orcidid></search><sort><creationdate>202106</creationdate><title>Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells</title><author>Xu, Zhipeng ; Zhang, Xiaoyun ; Chang, Hao ; Kong, Yue ; Ni, Yangyue ; Liu, Ran ; Zhang, Xiaolin ; Hu, Yang ; Yang, Zhi ; Hou, Min ; Mao, Rui ; Liu, Wen-Tao ; Du, Yasong ; Yu, Shunying ; Wang, Zhen ; Ji, Minjun ; Zhou, Zikai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p108t-2576c14f6147de525bd73f9e4406426357aee8dc9fa3b77af47defc7d0793ef63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adoptive Transfer - methods</topic><topic>Animals</topic><topic>Antigens, Protozoan - administration & dosage</topic><topic>Antigens, Protozoan - toxicity</topic><topic>Female</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Pregnancy</topic><topic>Prenatal Exposure Delayed Effects - immunology</topic><topic>Prenatal Exposure Delayed Effects - parasitology</topic><topic>Social Interaction</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - parasitology</topic><topic>Vocalization, Animal - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Zhipeng</creatorcontrib><creatorcontrib>Zhang, Xiaoyun</creatorcontrib><creatorcontrib>Chang, Hao</creatorcontrib><creatorcontrib>Kong, Yue</creatorcontrib><creatorcontrib>Ni, Yangyue</creatorcontrib><creatorcontrib>Liu, Ran</creatorcontrib><creatorcontrib>Zhang, Xiaolin</creatorcontrib><creatorcontrib>Hu, Yang</creatorcontrib><creatorcontrib>Yang, Zhi</creatorcontrib><creatorcontrib>Hou, Min</creatorcontrib><creatorcontrib>Mao, Rui</creatorcontrib><creatorcontrib>Liu, Wen-Tao</creatorcontrib><creatorcontrib>Du, Yasong</creatorcontrib><creatorcontrib>Yu, Shunying</creatorcontrib><creatorcontrib>Wang, Zhen</creatorcontrib><creatorcontrib>Ji, Minjun</creatorcontrib><creatorcontrib>Zhou, Zikai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Zhipeng</au><au>Zhang, Xiaoyun</au><au>Chang, Hao</au><au>Kong, Yue</au><au>Ni, Yangyue</au><au>Liu, Ran</au><au>Zhang, Xiaolin</au><au>Hu, Yang</au><au>Yang, Zhi</au><au>Hou, Min</au><au>Mao, Rui</au><au>Liu, Wen-Tao</au><au>Du, Yasong</au><au>Yu, Shunying</au><au>Wang, Zhen</au><au>Ji, Minjun</au><au>Zhou, Zikai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells</atitle><jtitle>Nature neuroscience</jtitle><addtitle>Nat Neurosci</addtitle><date>2021-06</date><risdate>2021</risdate><volume>24</volume><issue>6</issue><spage>818</spage><pages>818-</pages><eissn>1546-1726</eissn><abstract>Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii, a parasite that infects approximately two billion people, to induce MIA in mice. The adult male offspring showed autism-relevant behaviors and abnormal brain microstructure, along with a pro-inflammatory T-cell immune profile in the periphery and upregulation of interleukin-6 in brain astrocytes. We show that adoptive transfer of regulatory T (T
) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T
cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T
cells that constitute 32.6% of the pathogen-activated maternal T
population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T
cell transfer in neuropsychiatric disorders associated with immune alterations.</abstract><cop>United States</cop><pmid>33859437</pmid><doi>10.1038/s41593-021-00837-1</doi><orcidid>https://orcid.org/0000-0003-0293-0255</orcidid><orcidid>https://orcid.org/0000-0002-8853-5303</orcidid><orcidid>https://orcid.org/0000-0002-4577-9826</orcidid></addata></record> |
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| subjects | Adoptive Transfer - methods Animals Antigens, Protozoan - administration & dosage Antigens, Protozoan - toxicity Female HeLa Cells Humans Male Mice Mice, Inbred C57BL Pregnancy Prenatal Exposure Delayed Effects - immunology Prenatal Exposure Delayed Effects - parasitology Social Interaction T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - parasitology Vocalization, Animal - physiology |
| title | Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells |
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